Biomedical subjects

J A Balfour

Publications and source records attributed to J A Balfour.

At least 19 recordsLinked to original sources

PubMed1999

Ibandronate.

Ibandronate (ibandronic acid) is a third generation bisphosphonate which inhibits hone resorption in human and animal studies. It also inhibits bone formation only at high doses (10 microg/kg/day) in animal studies. In animal models, ibandronate was more potent than etidronate, clodronate, pamidronate and alendronate and equivalent in potency or more potent than risedronate in inhibiting induced hypercalcaemia and bone resorption. In clinical studies, single-dose ibandronate (0.2 to 6 mg intravenously) significantly reduced albumin-corrected serum calcium levels and urinary markers of bone resorption in patients with hypercalcaemia of malignancy, and in those with bone metastases. Serum calcium levels were normalised in 50 and 67% of ibandronate 2 mg recipients and in about 76% of 4 mg recipients. In postmenopausal women with osteoporosis or osteopenia. ibandronate (0.5 to 5 mg/day orally or 0.5 to 2 mg every 3 months intravenously) dose-dependently increased bone mineral density, with parallel reductions in the biochemical markers of bone turnover. In preliminary studies in patients with Paget's disease a single intravenous ibandronate dose (2mg) decreased serum alkaline phosphatase levels and urinary markers of bone turnover. Adverse events associated with the use of ibandronate in the management of hypercalcaemia of malignancy include increased body temperature, hypocalcaemia and hypophosphataemia. Less commonly, flu-like symptoms and gastrointestinal intolerance may occur.

Animals↗

PubMed1998

Brimonidine. A review of its pharmacological properties and clinical potential in the management of open-angle glaucoma and ocular hypertension.

Brimonidine is a highly selective alpha 2-adrenoceptor agonist which reduces intraocular pressure (IOP) by reducing aqueous humour production and increasing aqueous humour outflow via the uveoscleral pathway. Brimonidine is indicated for the topical management of open-angle glaucoma or ocular hypertension. In 3 large comparative studies in patients with open-angle glaucoma or ocular hypertension, the ocular hypotensive efficacy of brimonidine was maintained during treatment periods of up to 1 year. Mean reductions in peak (measured 2 hours after the morning dose) and trough (measured 12 hours after the evening dose) IOP were 5.6 to 5.9 and 3.3 to 3.7 mm Hg, respectively, after 3 or 12 months of treatment with brimonidine 0.2% twice daily. The efficacy of brimonidine in this setting was similar to that of timolol 0.5% twice daily at peak only (-6.0mm Hg), and superior to that of betaxolol 0.25% twice daily at both peak (-3.5mm Hg) and trough (-2.7mm Hg). When added to topical beta-adrenoceptor antagonist therapy, initial results showed brimonidine 0.2% twice daily to have additive ocular hypotensive efficacy similar to that of pilocarpine 2% 3 times daily. Thus, brimonidine 0.2% may be a useful adjunct in this setting. According to combined data from 2 large comparative studies, the most frequent adverse events associated with brimonidine therapy were oral dryness (30.0% of patients), ocular hyperaemia (26.3%) and ocular burning and/or stinging (24.0%). Ocular allergic reactions including allergic blepharitis, blepharoconjunctivitis and follicular conjunctivitis occurred with an incidence of 9.6% in 1 study. In a third comparative study, the incidence of adverse events associated with brimonidine therapy was lower, with conjunctival hyperaemia (11.4%) the most frequently reported event. Changes in systolic and diastolic blood pressure and, to a lesser extent, heart rate have been reported in patients treated with therapeutic doses of topical brimonidine for up to 12 months, but these changes were not clinically significant. Unlike beta-adrenoceptor antagonists, brimonidine is not contraindicated in patients with cardiopulmonary disease, although it should be used with caution in individuals with severe cardiovascular disease. Thus, further studies are warranted to determine the efficacy of brimonidine when used in combination with other glaucoma medications and its efficacy relative to newer drugs such as dorzolamide and latanoprost. However, available data suggest that brimonidine is a promising alternative option for the lowering of IOP in the management of open-angle glaucoma and ocular hypertension, particularly in patients with cardiopulmonary disease in whom topical beta-adrenoceptor antagonist therapy is contraindicated.

Adrenergic alpha-Agonists↗

PubMed1998

Raloxifene.

Raloxifene is a selective estrogen receptor modulator which mimics the effects of estrogens on bone and blood lipid levels without stimulatory effects on the breast or uterus. Raloxifene inhibits estrogen-dependent proliferation of human breast cancer cells in vitro and development of induced mammary tumours in rats in vivo. Raloxifene inhibits bone resorption induced by estrogen deficiency in murine and human studies and lowers serum cholesterol levels. In clinical studies in postmenopausal women, raloxifene 60 mg/day for 2 years significantly increased bone mineral density compared with placebo. In comparative clinical studies, raloxifene 60 mg/day had more modest effects than conjugated estrogens 0.625 mg/day on bone resorption and formation parameters and appeared to be less effective in increasing bone mineral density. In older postmenopausal women with existing bone fractures, raloxifene 60 or 120 mg/day for 1 year produced modest increases in bone mineral density. The most common treatment-related adverse events in raloxifene recipients were hot flushes and leg cramps. The risk of venous thromboembolic events is increased during raloxifene therapy. In contrast with conjugated estrogens 0.625 mg/day, raloxifene 200 or 600 mg/day for 8 weeks or 150 mg/day for 1 year did not produce endometrial proliferation.

Animals↗

PubMed1998

Risedronate.

Risedronate is a pyridinyl bisphosphonate that can be administered orally in lower dosages than other antiresorptive bisphosphonates. Like others of its class risedronate inhibits osteoclast-mediated bone resorption. In experimental models of osteoporosis, risedronate inhibited bone loss and improved trabecular architecture. In patients with Paget's disease, pain diminished or disappeared and serum alkaline phosphatase levels decreased after treatment with oral risedronate 30 mg/day for < or = 3 months. Risedronate 30 mg/day orally for 2 months significantly reduced pain, whereas etidronate 400 mg/day orally for 6 months tended to reduce pain, in a randomised double-blind trial of patients with Paget's disease. Oral risedronate 5 mg/day for < or = 2 years increased bone mass in postmenopausal women with low or normal bone mass. Risedronate 2.5 mg/day prevented bone loss in postmenopausal women treated with glucocorticoids for rheumatoid arthritis. The incidence of gastrointestinal or other adverse events was similar in patients treated with risedronate or placebo in clinical trials.

Animals↗

PubMed1998

Repaglinide.

Repaglinide is a novel insulin secretagogue being developed for the management of type 2 (non-insulin-dependent) diabetes mellitus. It stimulates release of insulin from the pancreatic beta-cell, but appears to bind to a different receptor site from sulphonylureas. Repaglinide lowers fasting and postprandial blood glucose levels in animals, healthy volunteers and patients with type 2 diabetes mellitus. Repaglinide is rapidly absorbed and eliminated, which may allow a relatively fast onset and offset of action. Excretion occurs almost entirely by non-renal mechanisms. In comparative clinical trials in patients with type 2 diabetes mellitus, repaglinide 0.5 to 4 mg twice or 3 times daily before meals provided similar glycaemic control to glibenclamide (glyburide) 2.5 to 15 mg/day. Addition of repaglinide to existing metformin therapy resulted in improved glycaemic control. In contrast with glibenclamide, use of repaglinide allowed patients to miss a meal without apparently increasing the risk of hypoglycaemia.

Animals↗

PubMed1998

Glimepiride. A review of its use in the management of type 2 diabetes mellitus.

UNLABELLED: Glimepiride is a sulphonylurea agent that stimulates insulin release from pancreatic beta-cells and may act via extrapancreatic mechanisms. It is administered once daily to patients with type 2 (non-insulin-dependent) diabetes mellitus in whom glycaemia is not controlled by diet and exercise alone, and may be combined with insulin in patients with secondary sulphonylurea failure. The greatest blood glucose lowering effects of glimepiride occur in the first 4 hours after the dose. Glimepiride has fewer and less severe effects on cardiovascular variables than glibenclamide (glyburide). Pharmacokinetics are mainly unaltered in elderly patients or those with renal or liver disease. Few drug interactions with glimepiride have been documented. In patients with type 2 diabetes, glimepiride has an effective dosage range of 0.5 to 8 mg/day, although there is little difference in efficacy between dosages of 4 and 8 mg/day. Glimepiride was similar in efficacy to glibenclamide and glipizide in 1-year studies. However, glimepiride appears to reduce blood glucose more rapidly than glipizide over the first few weeks of treatment. Glimepiride and gliclazide were compared in patients with good glycaemic control at baseline in a 14-week study that noted no differences between their effects. Glimepiride plus insulin was as effective as insulin plus placebo in helping patients with secondary sulphonylurea failure to reach a fasting blood glucose target level of < or = 7.8 mmol/L, although lower insulin dosages and more rapid effects on glycaemia were seen with glimepiride. Although glimepiride monotherapy was generally well tolerated, hypoglycaemia occurred in 10 to 20% of patients treated for < or = 1 year and > or = 50% of patients receiving concomitant insulin for 6 months. Pooled clinical trial data suggest that glimepiride may have a lower incidence of hypoglycaemia than glibenclamide, particularly in the first month of treatment. Dosage is usually started at 1 mg/day, titrated to glycaemic control at 1- to 2-week intervals to a usual dosage range of 1 to 4 mg/day (maximum 6 mg/day in the UK or 8 mg/day in the US). CONCLUSIONS: Glimepiride is a conveniently administered alternative to other sulphonylureas in patients with type 2 diabetes mellitus not well controlled by diet alone. Its possible tolerability advantages and use in combination with other oral antidiabetic drugs require further study. Glimepiride is also reported to reduce exogenous insulin requirements in patients with secondary sulphonylurea failure when administered in combination with insulin.

Blood Glucose↗

PubMed1998

Eprosartan.

Eprosartan is a nonpeptide angiotensin II receptor antagonist which has a high affinity for the AT1 receptor subtype. When administered at dosages of 400 to 800 mg/day (once or twice daily) for 13 weeks to patients with mild to moderate essential hypertension, eprosartan significantly reduced blood pressure compared with placebo. Eprosartan was at least as effective as enalapril 10 to 40 mg/day in a dose-titration study in patients with severe hypertension. Eprosartan is generally well tolerated; clinical trials have shown the drug to have a tolerability profile similar to that of placebo. As with other angiotensin II receptor antagonists, it does not cause cough. Eprosartan is not metabolised by the cytochrome P450 system and therefore has a low potential for drug interactions.

Acrylates↗

PubMed1998

Tolterodine.

Tolterodine is a competitive muscarinic receptor antagonist which has recently been launched for the treatment of overactive bladder. Tolterodine shows functional selectivity for the bladder over the salivary glands in vivo, which is not attributable to muscarinic receptor subtype selectivity. It is as potent as oxybutynin in inhibiting bladder contraction, but is much less potent in inhibiting salivation, suggesting that it may have less propensity to cause dry mouth in clinical use. In patients with overactive bladder, toleterodine significantly reduces the frequency of micturition and number of incontinence episodes, while increasing the average volume voided. The onset of pharmacological action of tolterodine is < 1 hour and therapeutic efficacy is maintained during long term treatment. In comparative trials, tolterodine and oxybutynin are equivalent in terms of efficacy. However, tolterodine is significantly better tolerated than oxybutynin, particularly with respect to the incidence and severity of dry mouth. No clinically relevant ECG changes have been noted with tolterodine.

Animals↗

PubMed1998

Levonorgestrel subdermal implants. A review of contraceptive efficacy and acceptability.

UNLABELLED: Levonorgestrel 6-capsule subdermal implants (Norplant) are an effective form of reversible contraception. When implanted under the skin of the upper arm, they release drug into the circulation at a relatively constant rate over 5 years. Generally, the cumulative pregnancy rate at the end of 5 years' levonorgestrel implant use is less than 2 per 100 users. The implants provide contraceptive efficacy equivalent to, or better than, that provided by other reversible methods (including oral contraceptives). Younger women are more likely than older women to become pregnant while using levonorgestrel implants. Bodyweight was positively correlated with risk of pregnancy in a number of studies, but may not be a factor with the currently available 6-capsule implant formulation. Limited data suggest that a new 2-rod levonorgestrel subdermal system (Jadelle) is as effective as the more extensively studied 6-capsule system and has a similar tolerability profile. Fertility returns rapidly after the implants are removed. Use of levonorgestrel subdermal implants is compatible with breast-feeding. In several studies, discontinuation rates were 2 to 15% during the first year of use; cumulative 5-year discontinuation rates ranged from 22 to 64 per 100 women. Despite a substantial incidence of adverse events during therapy, levels of user satisfaction are generally high. Menstrual abnormalities (increased or decreased menstrual flow, spotting, irregularity and amenorrhoea) affect most women at some time during therapy and are the most frequent reason for discontinuing levonorgestrel implants before the end of 5 years' treatment (incidence of 4.2 to 30.7 per 100 users). Mood changes and headache also may lead to discontinuation. Other reported adverse events include skin reactions (including acne), dizziness and weight gain. Serious adverse events (such as stroke, thrombotic thrombocytopenia and idiopathic intracranial hypertension) have been reported during levonorgestrel implants therapy, but the population incidence is difficult to calculate and causality is unclear. According to 3 pharmacoeconomic analyses from an institutional or managedcare perspective, all contraceptive interventions result in net cost savings. It is not clear whether levonorgestrel implants provide greater or smaller economic benefits than combined oral contraceptives. CONCLUSION: Levonorgestrel subdermal implants provide effective long term contraception. Despite a high incidence of menstrual adverse events, overall levels of user satisfaction are high, and 1-year continuation rates are better than those for combined oral contraceptives. Levonorgestrel subdermal implants are a good choice of contraceptive method in women who desire effective contraception, but who are unable to, or prefer not to, comply with an oral regimen.

Contraceptive Agents, Female↗

PubMed1998

Azithromycin. A review of its use in paediatric infectious diseases.

UNLABELLED: Azithromycin is an azalide antimicrobial agent active in vitro against major pathogens responsible for infections of the respiratory tract, skin and soft tissues in children. Pathogens that are generally susceptible to azithromycin include Haemophilus influenzae (including ampicillin-resistant strains), Moraxella catarrhalis, Chlamydia pneumoniae, Chlamydia trachomatis, Mycoplasma pneumoniae, Legionella spp., Streptococcus pyogenes and Streptococcus agalactiae. Azithromycin is also generally active against erythromycin- and penicillin-susceptible Streptococcus pneumoniae and methicillin-susceptible Staphylococcus aureus. Azithromycin is administered once daily, achieves clinically relevant concentrations at sites of infection, is slowly eliminated from the body and has few drug interactions. In children, azithromycin is usually given as either a 3-day course of 10 mg/kg/day or a 5-day course with 10 mg/kg on the first day, followed by 5 mg/kg/day for a further 4 days. These standard regimens were as effective as amoxicillin/clavulanic acid, clarithromycin, cefaclor and amoxicillin in the treatment of children with otitis media. Azithromycin was also as effective as either phenoxymethylpenicillin (penicillin V), erythromycin, clarithromycin or cefaclor against streptococcal pharyngitis or tonsillitis in children, but appears to result in more recurrence of infection than phenoxymethylpenicillin in this indication, necessitating a dosage of 12 mg/kg/day for 5 days. Community-acquired pneumonia, bronchitis and other respiratory tract infections in children responded as well to azithromycin as to amoxicillin/clavulanic acid, cefaclor, erythromycin or josamycin. Azithromycin was similar or superior to ceftibuten in mixed general practice populations of patients. However, symptoms of lower respiratory tract infections resolved more rapidly with azithromycin than with erythromycin, josamycin or cefaclor. Skin and soft tissue infections responded as well to azithromycin as to cefaclor, dicloxacillin or flucloxacillin, and oral azithromycin was as effective as ocular tetracycline in treating trachoma. Although not as well tolerated as phenoxymethylpenicillin in the treatment of streptococcal pharyngitis, azithromycin is at least as well tolerated as most other agents used to treat respiratory tract and other infections in children and was better tolerated than amoxicillin/clavulanic acid. Adverse events that do occur are mostly gastrointestinal and tend to be mild to moderate in severity. CONCLUSIONS: Azithromycin is an effective and well tolerated alternative to first-line agents in the treatment of respiratory tract, skin and soft tissue infections in children, offerring the convenience of a short, once-daily regimen.

Anti-Bacterial Agents↗

PubMed1998

Ofloxacin. A reappraisal of its use in the management of genitourinary tract infections.

UNLABELLED: Ofloxacin is an established fluoroquinolone agent which achieves good concentrations in genitourinary tract tissues and fluids. It has good in vitro activity against most Enterobacteriaceae, Staphylococcus saprophyticus, methicillin-susceptible S. aureus, Neisseria gonorrhoeae, Chlamydia trachomatis and Haemophilus ducreyi, intermediate activity against Ureaplasma urealyticum and most enterococci, but limited or no in vitro activity against enterococci, Serratia marcescens, Pseudomonas aeruginosa and many anaerobes. However, high concentrations achieved in the urine ensure its activity against most urinary tract pathogens. Ofloxacin demonstrates consistent efficacy in a broad range of urinary tract infections, achieving bacteriological response rates in excess of 80% in uncomplicated and 70% in complicated infections. The efficacy of ofloxacin was similar to that of all comparators tested including other fluoroquinolones, cephalosporins and cotrimoxazole (trimethoprim/sulfamethoxazole). Ofloxacin is also effective as a single-dose regimen in the treatment of uncomplicated gonorrhoea, as a 7-day regimen in uncomplicated C. trachomatis infections, and as monotherapy in uncomplicated pelvic inflammatory disease (PID). Again, ofloxacin demonstrated similar efficacy to alternative treatments in each type of infection. The availability of an intravenous formulation and near-complete oral bioavailability allow ofloxacin to be administered as a sequential regimen without loss of activity. The tolerability and drug interaction profile of ofloxacin is consistent with that of other fluoroquinolones. The most commonly reported adverse events with ofloxacin are gastrointestinal, neurological and dermatological. It was associated with a lower incidence of photosensitivity and tendinitis and higher incidence of some neurological events than some other fluoroquinolones. Ofloxacin seems to have a lower propensity to interact with xanthines than other fluoroquinolones. CONCLUSION: ofloxacin has established efficacy in the treatment of a wide variety of urinary tract infections, although, like other fluoroquinolones, it should be used rationally to preserve its activity. Currently, ofloxacin also holds an important place among fluoroquinolones in the treatment of C. trachomatis infections and uncomplicated PID, although its acceptance as monotherapy in PID is likely to depend on clarification of the causative role of anaerobic pathogens in this infection.

Anti-Infective Agents↗

PubMed1997

Dorzolamide. A review of its pharmacology and therapeutic potential in the management of glaucoma and ocular hypertension.

Dorzolamide (dorzolamide hydrochloride), the first topical carbonic anhydrase (CA) inhibitor to become available for clinical use, lowers intraocular pressure (IOP) by reducing aqueous humour formation. It is formulated as a 2% eyedrop for use in the management of glaucoma and ocular hypertension. When administered 3 times daily, dorzolamide is effective in lowering IOP in patients with open-angle glaucoma or ocular hypertension. Mean IOP was reduced by approximately 4 to 6 mm Hg at peak (2 hours postdose) and 3 to 4.5 mm Hg at trough (8 hours postdose) in clinical trails. A 1-year comparative study showed that the ocular hypotensive efficacy of dorzolamine 2% 3 times daily was similar to that of betaxolol 0.5% twice daily, but slightly inferior to that of timolol 0.5% twice daily. Dorzolamide has additive ocular hypotensive effects when used in conjunction with topical beta-adrenergic antagonists and was as effective as pilocarpine 2% 4 times daily as adjunctive therapy in patients receiving timolol. Dorzolamide does not appear to produce the acid-base or electrolyte disturbances and severe systemic adverse events associated with oral CA inhibitors, and unlike beta-adrenergic antagonists, it is not contraindicated in patients with asthma, reactive airways disease or heart disease. Furthermore, as CA inhibitors do not cause miosis, they may cause less interference with vision than pilocarpine or epinephrine (adrenaline). The most common adverse effects associated with dorzolamide are bitter taste and transient local burning or stinging. Conjunctivitis was the most common reason for discontinuation of dorzolamide in one large study. Thus, available data suggest that dorzolamide has potential as an alternative therapy option in patients with glaucoma or ocular hypertension who are intolerant of, or unable to receive, ophthalmic beta-adrenergic antagonists and as adjunctive therapy in patients already receiving these agents. Further efficacy and tolerability data are needed to determine the place of dorzolamide in therapy.

Absorption↗

PubMed1997

Estradiol and dydrogesterone. A review of their combined use as hormone replacement therapy in postmenopausal women.

The focus of this review is hormone replacement therapy (HRT) with continuous oral 17 beta-estradiol (herein referred to as estradiol) 2 mg/day plus sequential oral dydrogesterone 10 or 20 mg/day for 14 days of each 28-day cycle. According to data from nonblind trials, this regimen relieves climacteric symptoms, preserves bone mineral density (BMD) and improves the cardiovascular risk profile in postmenopausal women. Increases in mean BMD in the lumbar spine of 2.4 to 6.4% have been reported after 2 years' treatment. The effect on BMD of oral estradiol plus sequential dydrogesterone was similar to that achieved with transdermal estradiol plus sequential oral dydrogesterone or with oral tibolone. Good protection against endometrial hyperplasia and cancer is provided by the dydrogesterone component. Cyclical vaginal bleeding occurs in most treatment cycles, but is generally light to moderate and the time of onset is highly predictable. Noncyclical bleeding occurs in < 10% of cycles. Mean serum high density lipoprotein-cholesterol levels are increased and low density lipoprotein-cholesterol levels are decreased during treatment with oral estradiol plus sequential dydrogesterone. Insulin resistance appears to be improved. Blood pressure and bodyweight are not generally affected to any clinically important extent. Serum homocysteine levels were reported to decrease in postmenopausal women with high pretreatment levels. No data are available on the general tolerability profile of this regimen. However, the adverse events that most commonly led to discontinuation of treatment in clinical trials were typical of those associated with HRT, including vaginal bleeding headache, bloating and breast tenderness. Although the risk of breast cancer has not been specifically assessed for this regimen, it is unlikely to carry a greater risk than that of other HRT regimens. In summary available data indicate that treatment with continuous oral estradiol plus sequential dydrogesterone is effective in relieving climacteric symptoms and preserving BMD in postmenopausal women. The dydrogesterone component provides good endometrial protection and cycle control without negating the cardiovascular benefits of estradiol. Comparisons with other standard HRT regimens and long term data (including clinical end-points) are needed. In the meantime, this regimen can be regarded as an acceptable HRT option.

Aged↗

PubMed1997

Fosfomycin tromethamine. A review of its antibacterial activity, pharmacokinetic properties and therapeutic efficacy as a single-dose oral treatment for acute uncomplicated lower urinary tract infections.

Fosfomycin tromethamine is a phosphonic acid bactericidal agent with in vitro activity against most urinary tract pathogens. It is particularly active against Escherichia coli, and Citrobacter, Enterobacter, Klebsiella, Serratia and Enterococcus spp. There appears to be little cross-resistance between fosfomycin and other antibacterial agents, possibly because it differs from other agents in its general chemical structure and site of action. In its new formulation as the oral tromethamine salt, fosfomycin has 34 to 41% oral bioavailability, has a mean elimination half-life of 5.7 hours, and is primarily excreted unchanged in the urine. Following a single 3 g oral dose, peak urinary concentrations occur within 4 hours and remain high (> 128 mg/L) for 24 to 48 hours, which is sufficient to inhibit most urinary tract pathogens. In clinical trials in patients with acute uncomplicated lower urinary tract infection, single-dose fosfomycin tromethamine therapy was effective, and comparable with several other antibacterial agents given either as single-dose or multiple-dose treatments [e.g. beta-lactam and fluoroquinolone agents, cotrimoxazole (trimethoprim-sulfamethoxazole), nitrofurantoin and pipemidic acid]. Bacteriological eradication rates of 75 to 90% were achieved 5 to 11 days after therapy, with eradication rates of 62 to 93% 4 to 6 weeks after therapy. In 3 large double-blind comparisons with ciprofloxacin, cotrimoxazole and nitrofurantoin, 99% of fosfomycin tromethamine recipients and 100% of patients receiving comparator agents were considered clinically cured or improved after therapy. Fosfomycin tromethamine is well tolerated, with a low incidence of adverse events. These comprise mainly gastrointestinal symptoms that are transient, mild and self-limiting. Thus, fosfomycin tromethamine achieves high clinical and bacteriological cure rates in patients with acute uncomplicated lower urinary tract infection and is well tolerated. The single-dose administration regimen and favourable US pregnancy category rating of fosfomycin tromethamine should also encourage its use in this indication.

Acute Disease↗

PubMed1997

Grepafloxacin.

Grepafloxacin (OPC-17116) is a new once-daily fluoroquinolone antimicrobial agent which appears to have high tissue penetration and the wide spectrum of antimicrobial activity typical of this class of agents, but with improved activity against Gram-positive organisms, notably Streptococcus pneumoniae. The in vitro activity of grepafloxacin was similar to or slightly lower than that of ciprofloxacin against Enterobacteriaceae but better than that of ciprofloxacin against most Gram-positive organisms. In particular, grepafloxacin showed good activity against pathogens implicated in community-acquired pneumonia, with 4-fold higher potency than ciprofloxacin against S. pneumoniae, including penicillin-resistant strains. In animal studies, grepafloxacin did not induce convulsions when administered at high doses in conjunction with nonsteroidal anti-inflammatory agents. Grepafloxacin has a weak propensity for causing phototoxicity, similar to that of ciprofloxacin. In comparative clinical trials, grepafloxacin demonstrated similar efficacy to amoxicillin in community-acquired pneumonia, ofloxacin in pneumonia and chronic respiratory tract infection, and cefixime in uncomplicated gonococcal urethritis and gonococcal cervicitis. Grepafloxacin has also shown clinical efficacy in preliminary studies in patients with chlamydial endocervical infection or bacillary dysentery.

Anti-Infective Agents↗

PubMed1997

Tacalcitol.

Tacalcitol is a vitamin D3 analogue which is available in Japan as a 2 micrograms/g ointment for twice daily application and in Western markets as a 4 micrograms/g ointment for once daily application. Tacalcitol inhibits proliferation, and induces the differentiation, of keratinocytes. In addition, it appears to modulate inflammatory and immunological mediators in the skin which may be involved in the aetiology of psoriasis. No significant systemic drug absorption occurs after application of tacalcitol to the skin. Results of clinical trials indicate that topical tacalcitol is effective in the management of stable plaque psoriasis (and possibly pustular forms of the disease), and has a similar efficacy to topical betamethasone valerate in this setting. Application of tacalcitol ointment 4 micrograms/g once daily for up to 8 weeks did not cause hypercalcaemia or hypercalciuria. Mild local skin irritation has been reported in a variable proportion of patients (< or = 12%).

Cholecalciferol↗

PubMed1997

Dolasetron. A review of its pharmacology and therapeutic potential in the management of nausea and vomiting induced by chemotherapy, radiotherapy or surgery.

Dolasetron (dolasetron mesilate) is a pseudopelletierine-derived 5-HT3 antagonist which has recently become available for clinical use. It is rapidly converted in vivo to its active major metabolite, hydrodolasetron, which appears to be largely responsible for its pharmacological activity. In clinical trials, single intravenous or oral doses of dolasetron were effective in preventing acute chemotherapy-induced nausea and vomiting (CINV). Intravenous doses of 1.8 mg/kg achieved complete suppression of vomiting in approximately 50% of patients receiving highly emetogenic cisplatin-containing chemotherapy and in approximately 60 to 80% of patients receiving moderately emetogenic chemotherapy. In the latter setting, oral doses of 200 mg achieved similar response rates. In comparative studies, intravenous dolasetron 1.8 mg/kg was as effective as intravenous granisetron 3 mg or ondansetron 32 mg after highly emetogenic chemotherapy, and oral dolasetron 200 mg was equivalent to multiple oral doses of ondansetron (3 or 4 doses of 8 mg) after moderately emetogenic chemotherapy. Dolasetron 1.8 mg/kg was superior to metoclopramide in preventing emesis induced by high dose cisplatin or by moderately emetogenic chemotherapy in high risk subgroups. Dolasetron has also shown efficacy in preventing radiotherapy-induced nausea and vomiting (RINV) in preliminary studies. Single intravenous or oral dolasetron doses ranging from 12.5 to 100 mg and 25 to 200 mg, respectively, were significantly more effective than placebo in preventing postoperative nausea and vomiting (PONV) in female surgical patients. A 50 mg intravenous dose was as effective in preventing PONV as ondansetron 4 mg in a mixed-gender group. Intravenously administered dolasetron was also effective in treating established PONV, although complete suppression of vomiting was achieved in < 40% of patients. Dolasetron has a tolerability profile characteristic of this class of compounds, with headache, dizziness and diarrhoea being the most commonly occurring adverse events in clinical trials. Diarrhoea is not thought to be related to dolasetron administration, being experienced mostly by patients receiving chemotherapy. Dolasetron and other 5-HT3 receptor antagonists have been associated with minor changes in ECG intervals, but these generally do not appear to be clinically important. Thus, available evidence suggests that dolasetron will provide an alternative to other 5-HT3 receptor antagonists for the management of CINV and PONV. Further studies are required to determine whether it offers any advantages over other agents in these settings and to determine the optimum dosage for preventing RINV.

Administration, Oral↗

PubMed1996

Intracavernous alprostadil. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in erectile dysfunction.

Intracavernous alprostadil (synthetic prostaglandin E1) is a vasodilating agent which acts by relaxing the smooth muscles of the corpus cavernosum and by increasing the diameter of cavernous arteries; this leads to erection. Following intracavernous administration, alprostadil is either locally metabolised or rapidly cleared from the penis into the systemic circulation where it is extensively metabolised by the lungs. Studies suggest that long term use of intracavernous alprostadil may increase penile blood flow, although the clinical relevance of this is not currently known. In men with erectile dysfunction (ED), short term trials have shown that intracavernous alprostadil is superior or equal, in inducing erections, to other intracavernous agents such as papaverine, the combination of papaverine plus phentolamine, linsidomine and topical nitroglycerin (glyceryl trinitrate). Intracavernous alprostadil induced erections in around 70% of patients with ED of various origins in short term studies. 49 to 84% of patients accept the offer of joining self-injection programmes and 13 to 60% of these patients withdraw from such programmes for a variety of reasons. At therapeutic doses, intracavernous alprostadil is well tolerated. The most common adverse event of transient penile pain occurred in around one-third of patients and in 11% of injections, causing 3 to 5% of patients to withdraw from self-injection programmes. Potentially serious adverse events such as priapism and fibrosis occurred in 4 and 8% of patients. Overall, available data suggest that the efficacy of intracavernous alprostadil is superior or equal to that of other erectogenic agents which are in use. Furthermore, the drug is well tolerated especially with regard to serious adverse events. Thus, although further research is necessary to confirm its use in combination with other agents, alprostadil appears likely to become the intracavernous agent of choice for the management of erectile dysfunction.

Alprostadil↗