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Biomedical subjects

S M Abdel-Rahman

Publications and source records attributed to S M Abdel-Rahman.

At least 19 recordsLinked to original sources
PubMed1999

Stability of fumagillin in an extemporaneously prepared ophthalmic solution.

The stability of fumagillin 70 microg/mL (as the bicyclohexylammonium crystal) in an extemporaneously prepared ophthalmic solution was studied. An ophthalmic solution of fumagillin 70 microg/mL was prepared by combining 120 mg of fumagillin bicyclohexylammonium crystals with 20 mL of 0.9% Sodium Chloride Injection, USP, and 20 mL of an ophthalmic irrigating solution. The solution was stored in 12 sterile semi-opaque dropper bottles; 4 bottles were stored at 25 degrees C exposed to light, 4 were stored at 25 degrees C in the dark, and 4 were stored at 4 degrees C in the dark. Samples were taken on days 0, 7, 14, 21, and 28 and analyzed by high-performance liquid chromatography. Sterility was tested as well. In the solutions stored at 25 degrees C, 17-30% of the initial drug concentration was lost during the first week. The solution protected from light and stored at 4 degrees C lost about 12% of active drug by week 4. There was no change in color or odor in any of the solutions and only a minor change in pH over the study period. There was no evidence of microbial growth in any of the solutions tested. Fumagillin 70 microg/mL (as the bicyclohexylammonium crystal) in 0.9% sodium chloride injection and an ophthalmic irrigating solution containing benzalkonium chloride was stable in the dark for 14 days at 4 degrees C.

Antiprotozoal Agents↗
PubMed1999

Stability of terbinafine hydrochloride in an extemporaneously prepared oral suspension at 25 and 4 degrees C.

The stability of terbinafine 25 mg/mL (as the hydrochloride salt) in an extemporaneously prepared oral suspension at 25 and 4 degrees C was studied. Twenty 250-mg terbinafine tablets were crushed to a fine powder and diluted to a concentration of 25 mg/mL with sweetened vehicle. The suspension was stored in amber polyethylene prescription bottles at 25 or 4 degrees C. Samples were taken on days 0, 7, 14, 28, 42, 56, 70, and 91 for duplicate analysis of terbinafine content by high-performance liquid chromatography and to observe any changes in color and odor; pH was measured as well. Through the initial 42 days, the mean concentration of terbinafine in the samples stored at both temperatures was >93% of the initial concentration; by day 56, the mean concentration was <88%. No appreciable changes in color or odor were observed during the study period. The apparent pH of the suspension decreased slightly over the 91 days, from an initial 5.6 to 5.5. Terbinafine 25 mg/mL (as the hydrochloride salt) in an extemporaneously prepared oral suspension was stable for up to 42 days in polyethylene prescription bottles at 25 and 4 degrees C.

Administration, Oral↗
PubMed1999

Investigation of terbinafine as a CYP2D6 inhibitor in vivo.

BACKGROUND: Terbinafine is an orally active antifungal used in the treatment of dermatophytoses. To date, studies evaluating the effect of terbinafine on the cytochromes P450 have failed to show any significant interactions. This prospective open-label study was designed to confirm our previous finding that terbinafine may inhibit CYP2D6. METHODS: Nine healthy volunteers were enrolled in this study-6 genotypically consistent with an extensive metabolizer phenotype and 3 genotypic poor metabolizers for CYP2D6. The change in CYP2D6 enzyme activity before (x 3) and after (monthly x 6 months) administration of terbinafine (250 mg once daily x 14 days) was evaluated with the dextromethorphan to dextrorphan urinary metabolite ratios. On each study day a predose urine sample was collected, 0.3 mg/kg dextromethorphan was administered, and urine was collected for 24 hours. Dextromethorphan and its metabolites were quantified from urine by HPLC. RESULTS: Baseline phenotype values were concordant with individual genotype. In all extensive metabolizers, the administration of terbinafine resulted in a dramatic increase in the dextromethorphan/dextrorphan ratio, converting 4 of the 6 extensive metabolizers into phenotypic poor metabolizers. On average, a 97-fold increase in ratio (range, 35 to 265) was observed for extensive metabolizers after the administration of terbinafine. No significant change was observed in the metabolite ratios of poor metabolizers during the course of the study. CONCLUSIONS: Terbinafine inhibits CYP2D6 sufficiently to produce a discordance between genotype and phenotype for the enzyme. The dextromethorphan/dextrorphan metabolite ratios increased in all individuals, with otherwise functional CYP2D6 activity. The disposition of CYP2D6 substrates coadministered with terbinafine may be significantly altered in extensive metabolizers for this cytochrome P450 isoform, who comprise approximately 93% of the population.

Adult↗
PubMed1999

Single-dose pharmacokinetics of a pleconaril (VP63843) oral solution in children and adolescents. Pediatric Pharmacology Research Unit Network.

Pleconaril is an orally active, broad-spectrum antipicornaviral agent which demonstrates excellent penetration into the central nervous system, liver, and nasal epithelium. In view of the potential pediatric use of pleconaril, we conducted a single-dose, open-label study to characterize the pharmacokinetics of this antiviral agent in pediatric patients. Following an 8- to 10-h period of fasting, 18 children ranging in age from 2 to 12 years (7.5 +/- 3.1 years) received a single 5-mg/kg of body weight oral dose of pleconaril solution administered with a breakfast of age-appropriate composition. Repeated blood samples (n = 10) were obtained over 24 h postdose, and pleconaril was quantified from plasma by gas chromatography. Plasma drug concentration-time data for each subject were fitted to the curve by using a nonlinear, weighted (weight = 1/Ycalc) least-squares algorithm, and model-dependent pharmacokinetic parameters were determined from the polyexponential parameter estimates. Pleconaril was well tolerated by all subjects. A one-compartment open-model with first-order absorption best described the plasma pleconaril concentration-time profile in 13 of the subjects over a 24-h postdose period. Pleconaril pharmacokinetic parameters (means +/- standard deviations) for these 13 patients were as follows. The maximum concentration of the drug in serum (Cmax) was 1,272.5 +/- 622.1 ng/ml. The time to Cmax was 4.1 +/- 1.5 h, and the lag time was 0.75 +/- 0.56 h. The apparent absorption rate constant was 0.75 +/- 0.48 1/h, and the elimination rate constant was 0.16 +/- 0.07 1/h. The area under the concentration-time curve from 0 to 24 h was 8,131.15 +/- 3,411.82 ng.h/ml. The apparent total plasma clearance was 0.81 +/- 0.86 liters/h/kg, and the apparent steady-state volume of distribution was 4.68 +/- 2.02 liters/kg. The mean elimination half-life of pleconaril was 5.7 h. The mean plasma pleconaril concentrations at both 12 h (250.4 +/- 148.2 ng/ml) and 24 h (137.9 +/- 92.2 ng/ml) after the single 5-mg/kg oral dose in children were higher than that from in vitro studies reported to inhibit > 90% of nonpolio enterovirus serotypes (i.e., 70 ng/ml). Thus, our data support the evaluation of a 5-mg/kg twice-daily oral dose of pleconaril for therapeutic trials in pediatric patients with enteroviral infections.

Administration, Oral↗
PubMed1999

Single oral dose escalation pharmacokinetics of pleconaril (VP 63843) capsules in adults.

Pleconaril is an orally active broad-spectrum antipicornaviral agent with excellent penetration into the central nervous system and nasal epithelium. The authors report the results of a randomized, placebo-controlled, dose escalation study of pleconaril oral capsules following single-dose administration of 50 to 1000 mg. Fifty-six healthy adults (ages 19-55) participated in the study. Each subject received a single dose of pleconaril oral capsule(s) or an identically matched placebo. Blood samples (n = 19) were obtained over 36 hours postdose, and pleconaril was quantified from plasma by gas chromatography. Pleconaril disposition was best characterized using a two-compartment open-model with first-order absorption. Fifty-five subjects completed the study (31 +/- 10 years, 77.6 +/- 11 kg). The administration of pleconaril was well tolerated. There was no difference in tmax, lambda z, ka, t1/2elim, Cl/F, or Vdss/F among the various dose groups. A significant difference in both Cmax and AUC was observed between study groups; however, this difference became insignificant when the parameters were corrected for dose. Cmax and AUC were dose proportional between 50 and 1000 mg (r2 > 0.97 and 0.90, respectively). Pleconaril demonstrates a favorable safety and pharmacokinetic profile following single-dose administration.

Administration, Oral↗
PubMed1998

Efficacy of itraconazole in children with Trichophyton tonsurans tinea capitis.

BACKGROUND: Tinea capitis is prevalent in children. Although widely used as the drug of choice, the response to griseofulvin may be incomplete and an extended duration of therapy is often required. The response to newer antifungals has not been methodically evaluated in children with Trichophyton tonsurans infection. OBJECTIVE: Our purpose was to determine the efficacy of itraconazole in children with tinea capitis caused by T. tonsurans. METHODS: Pediatric patients with culture proven tinea capitis were enrolled from a hospital-based primary care clinic between January and December of 1996. Patients were treated with itraconazole 100 mg/day and a selenium sulfide-containing shampoo for 4 weeks. Children were evaluated mycologically and clinically every 2 weeks for 2 months. Patients were considered successfully treated if they were culture negative and clinically improved at the end of the study period. Children who remained culture positive or who were clinically not improved at 2 months were classified as treatment failures and retreated. RESULTS: Twenty-five patients completed the study, and 10 (40%) were successfully treated. Fifteen children required re-treatment: 14 remained culture positive at week 8, and one was mycologically negative but clinically worse. CONCLUSION: Itraconazole at a dose of 100 mg/day for 4 weeks may be effective in less than half of children with T. tonsurans tinea capitis.

Antifungal Agents↗
PubMed1998

Cefpodoxime pharmacokinetics in children: effect of food.

BACKGROUND: Cefpodoxime, an oral third generation cephalosporin antibiotic, is used for the treatment of acute upper respiratory tract infection caused by susceptible bacteria in children 5 months to 12 years of age. We report the results of a randomized two-way crossover study designed to characterize the disposition of a single dose (10 mg/kg) of cefpodoxime proxetil oral suspension in children, under fed and fasted conditions. METHODS: Seventeen children (8.4 months to 12.2 years old, seven female) participated in this study. Each subject received a single 10-mg/kg dose of cefpodoxime proxetil oral suspension, after a predose fast and again coadministered with food. Repeated blood samples (n=10) were obtained during 12 h postdose and cefpodoxime was quantified from plasma by high performance liquid chromatography. Plasma concentration vs. time data were curve fit for each subject with a nonlinear weighted least squares algorithm, and pharmacokinetic parameters were determined from the polyexponential estimates. RESULTS: Cefpodoxime disposition was best characterized using a one-compartment open model with first order absorption. The area under the plasma concentration vs. time curve, Cmax and Ke were not significantly different between fed and fasted conditions. However, Tmax was significantly prolonged (fed=2.79+/-1.10 h vs. fasted=1.93+/-0.54 h) and Ka was significantly smaller (fed=0.42+/-0.14 h(-1) vs. fasted=0.81+/-0.72 h(-1)) in the fed state. CONCLUSIONS: Administration of cefpodoxime in the presence of food affected the rate but not the extent of absorption. Cefpodoxime proxetil oral suspension can be administered without regard to meals in children 6 months to 12 years of age.

Area Under Curve↗
PubMed1998

Single-dose pharmacokinetics of a pleconaril (VP63843) oral solution and effect of food.

Pleconaril is an orally active broad-spectrum antipicornaviral agent which demonstrates excellent penetration into the central nervous system, liver, and nasal epithelium. We report the results of a randomized two-way crossover study designed to characterize the disposition of a single dose (200 mg) of pleconaril oral solution in fed and fasting humans. Twelve healthy adult subjects (18.7 to 39 years of age) participated in this study. Each subject received a single 200-mg dose of pleconaril oral solution, both coadministered with a standard English breakfast and following a 10-h predose fast. There was a minimum 7-day washout period between pleconaril doses. Repeated blood samples (n = 10) were obtained over 24 h postdose, and the pleconaril level in plasma was quantified by gas chromatography. Plasma concentration-versus-time data were curve fitted for each subject by using a nonlinear weighted least-squares algorithm, and pharmacokinetic parameters were determined from the polyexponential estimates. Pleconaril disposition was best characterized by a one-compartment open model with first-order absorption. The apparent bioavailability of pleconaril oral solution was significantly increased with the administration of food. The area under the concentration-time curve and maximum concentration of pleconaril in plasma achieved following the standard English breakfast (i.e., 9.08 +/- 3.23 mg/liter . h and 1.14 +/- 0.58 mg/liter, respectively) were 2.2- and 2.5-fold higher, respectively than those achieved in the fasting state (i.e., 4.08 +/- 2.74 mg/liter . h and 0.46 +/- 0.30 mg/liter, respectively). Mean plasma pleconaril concentrations 12 h after a single 200-mg oral dose (fed, 0.25 +/- 0.2 mg/liter; fasting, 0.11 +/- 0.10 mg/liter) in healthy adults remained greater than that required to inhibit more than 90% of the enteroviruses in cell culture (i.e., 0.07 mg/liter). To enhance the oral bioavailability of pleconaril, coadministration with a fat-containing meal is recommended.

Administration, Oral↗
PubMed1998

Evaluation of a diagnostic monoclonal antibody-based capture enzyme-linked immunosorbent assay for detection of a 26- to 28-kd Fasciola hepatica coproantigen in cattle.

OBJECTIVE: To develop a monoclonal antibody-based capture ELISA for detection of a 26- to 28-kd coproantigen of Fasciola hepatica in the feces of infected cattle. ANIMALS: 27 crossbred yearling calves, 2 New Zealand White rabbits. PROCEDURE: A capture ELISA that uses a previously described monoclonal antibody (MAB) M2D5/D5F10 was developed. The MAB was used to capture the antigen from the feces, and hyperimmune rabbit serum raised against the purified 26- to 28-kd glycoprotein was used to detect the coproantigen. This test was used for the detection of the antigen in the feces of 27 experimentally infected calves with known numbers of flukes. Fecal specimens obtained before infection from the same calves were used as negative controls. RESULTS: The assay results identified all calves infected with more than 10 flukes at necropsy, and as little as 300 pg of coproantigen/ml of fecal supernatant was detected. The assay results correlated well with the number of flukes, suggesting that it is possible to estimate fluke burden. Infections as early as 6 weeks duration were detected, before flukes mature to adults and start to shed eggs. CONCLUSIONS: In experimentally infected calves, the coproantigen capture ELISA was more sensitive and easier to perform than microscopic examination for the diagnosis of F hepatica infection; moreover, 6-week-old prepatent infections were detectable. CLINICAL RELEVANCE: This capture ELISA containing an F hepatica 26- to 28-kd coproantigen is a quantitative assay that is more sensitive than fecal egg counting. In addition, the assay is rapid, easy to perform and lends itself well to large numbers of samples. Because it is antigen based, the ELISA may be useful for diagnosis of F hepatica infection in other species, including human beings.

Animals↗
PubMed1997

Treatment of tinea capitis.

OBJECTIVE: To review the epidemiology, pathogenesis, mycology, clinical presentation, and pharmacotherapy of tinea capitis, and describe the role of newer antimycotic agents. DATA SOURCES: A MEDLINE search restricted to English-language articles published from 1966 through 1996 and journal references were used in preparing this review. DATA EXTRACTION: The data on mycology, pharmacokinetics, adverse effects, and drug interactions were obtained from controlled studies and case reports appearing in the literature. Both open-label and comparative studies were evaluated to assess the efficacy of antimycotics in the treatment of this infection. DATA SYNTHESIS: Griseofulvin is the drug of choice in the treatment of tinea capitis. Newer agents with greater efficacy or shorter treatment durations continue to be explored. Ketoconazole, the first azole studied for efficacy in tinea capitis, has not demonstrated any clinical advantage over griseofulvin in several controlled clinical trials. Itraconazole is effective, but the available data are limited to case reports and a single uncontrolled study. Terbinafine similarly has shown promise in the treatment of tinea capitis, but the oral formulation was only recently approved in the US. Existing studies reflect the results in infection with pathogens not seen in the US. Both itraconazole and terbinafine achieve high concentrations in the hair and stratum corneum that persist for several weeks following drug administration. This may enable shorter courses of therapy; however, comparative studies need to be conducted in the US. CONCLUSIONS: Tinea capitis remains the most common dermatophyte infection in young urban children. Oral antifungal therapy is required for effective treatment, often for several months. The combination of griseofulvin with a selenium sulfide shampoo continues to be the mainstay of therapy until more experience is gained with the newer antimycotics.

Administration, Oral↗
PubMed1997

Response to initial griseofulvin therapy in pediatric patients with tinea capitis.

OBJECTIVE: To estimate the response rate to initial griseofulvin therapy in pediatric patients with tinea capitis and to determine whether clinical or epidemiologic variables differed between patients responding positively and negatively to therapy. METHODS: A review of patients' medical records with a confirmed diagnosis of tinea capitis was performed retrospectively over a 2-year period. Patients were included only if a positive dermatophyte culture was obtained and the initial prescription for griseofulvin was filled at our pharmacy. Responders were children not returning to the clinic or returning without signs or symptoms of infection. Nonresponders were those returning within 8 months with signs and symptoms of disease, requiring additional therapy. RESULTS: During July 1993-June 1995, 479 positive fungal cultures were confirmed in 474 patients, and 857 prescriptions for griseofulvin were filled for 765 patients at our institution. Of 122 evaluable patients meeting both criteria, 60.7% were classified as responders to initial prescribed therapy. The remaining 39.3% returned to the clinic within 8 months of initial therapy, requiring additional treatment. An additional 10.7% had a recurrence at a later date. There was no correlation between clinical response and dosage, age, race, or gender, although there was a trend toward longer treatment duration among responders. CONCLUSIONS: It is evident that tinea capitis persists in the urban pediatric population. Our data suggest that griseofulvin, the current drug of choice, may be ineffective in at least one-third of pediatric patients with tinea capitis.

Age Factors↗
PubMed1997

Oral terbinafine: a new antifungal agent.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines of terbinafine. Available comparative data of terbinafine and other antimycotic agents are described for understanding the potential role of terbinafine in patient care. DATA SOURCES: A MEDLINE search restricted to English language during 1966-1996 and extensive review of journals was conducted to prepare this article. MeSH headings included allylamines, terbinafine, SF 86-327, dermatophytosis, dermatomycosis. DATA EXTRACTION: The data on pharmacokinetics, adverse effects, and drug interactions were obtained from open-label and controlled studies and case reports. Controlled single- or double-blind studies were evaluated to describe the efficacy of terbinafine in the treatment of various fungal infections. DATA SYNTHESIS: Terbinafine is the first oral antimycotic in the allylamines class: a fungicidal agent that inhibits ergosterol synthesis at the stage of squalene epoxidation. Terbinafine demonstrates excellent in vitro activity against the majority of dermatophyte species including Trichophyton rubrum, Trichophyton mentagrophytes, and Epidermophyton floccosum; less activity is seen against Dematiaceae and the filamentous fungi. It is least active against the pathogenic yeast and this correlates with the relatively poor efficacy against these organisms in vivo. High concentrations of terbinafine are achieved in keratinous tissues, the site of superficial infections, and these concentrations are maintained for up to 3 months. The clinical efficacy of terbinafine against a number of dermatophyte infections exceeds that of the current standard of therapy, griseofulvin. The efficacy of terbinafine may be as good or better than that of the azole antifungals. Additional studies are required to confirm these observations. Terbinafine demonstrates a good safety profile, and relatively few drug interactions have been identified. CONCLUSIONS: Terbinafine is more effective than the gold standard, griseofulvin, in the treatment of tinea pedis and tinea unguinum, with considerably shorter treatment duration in the latter. It has been proven as effective as griseofulvin in the treatment of tinea capitis, tinea corporis, and tinea cruris. Terbinafine does not appear to offer any advantage in the treatment of nondermatophyte infections; its utility in the treatment of systemic infections has yet to be established. Depending on individual institutional costs, terbinafine may be a front-line drug for some superficial infections responding poorly to the current standard of therapy.

Antifungal Agents↗
PubMed1997

Guidelines for the treatment of Helicobacter pylori in the pediatric population.

Several factors including long-term eradication of the organism, cost, compliance, and adverse event profile should be considered for treating H. pylori infection in pediatric patients. Triple therapy with bismuth, tetracycline, and metronidazole is considered the gold standard for adult patients; however, tetracyclines are not recommended in children younger than 8 years due to the potential for tooth discoloration and alterations in bone growth. Dual and shorter duration of therapy should be evaluated in children with H. pylori. The new dual therapy omeprazole/clarithromycin regimens approved by the Food and Drug Administration for adults may be considered as an alternative for children when concerns include the use of salicylates or allergy to beta-lactams. Although the dosage of omeprazole in pediatric patients has not been established (no pediatric formulation exists), clarithromycin is available for use in pediatric patients. However, these drugs cannot be recommended for children with H. pylori until additional studies in this population are available. Based on the available data, aminopenicillin/bismuth or aminopenicillin/tinidazole combinations appear to be effective in eradicating H. pylori in children. Amoxicillin 50 mg/kg/d plus bismuth subsalicylate (< 10 y, 262 mg; > 10 y, 525 mg qid) or bismuth subcitrate (< 12 y, 120 mg; > 12 y, 240 mg bid) can be used for 6 weeks. The bismuth dosages represented above were those used in various studies. It should be realized, however, that a definitive dosage of bismuth subsalicylate for children in the treatment of H. pylori has not been established. The adult dosage of bismuth subsalicylate for the eradication of H. pylori is the same as that used for prophylaxis in diarrhea (525 mg qid). When dosage of this agent is unknown (particularly for the treatment of very young children), the use of established dosages for prophylaxis in diarrhea may be considered for treating H. pylori. Additionally, bismuth subsalicylate should be used with caution in children with suspected viral infections (i.e., to prevent Reye's syndrome) or those receiving concurrent therapy with interacting drugs. If available, tinidazole 20 mg/kg/d can be used with amoxicillin 50 mg/kg/d for 6 weeks to treat children infected with H. pylori.

Adolescent↗
PubMed1996

Dirithromycin: a new macrolide.

OBJECTIVE: To review the clinical microbiology and therapeutic use of dirithromycin, emphasizing comparative data between dirithromycin and the standard macrolide erythromycin, as well as clarithromycin and azithromycin. DATA SOURCES: A MEDLINE search of English-language literature during the years 1966-1996, and an extensive review of journals were conducted to prepare this article. DATA EXTRACTION: The data on pharmacokinetics, adverse effects, and drug interactions were obtained from open and controlled studies. Controlled single- or double-blind studies were evaluated to assess the efficacy of dirithromycin in the treatment of various upper and lower respiratory tract infections, as well as skin and soft tissue infections. DATA SYNTHESIS: The spectrum of activity of dirithromycin is similar to that of erythromycin, clarithromycin, or azithromycin, with some notable exceptions. Dirithromycin was more active in vitro against Campylobacter jejuni and Borrelia burgdorferi than was erythromycin or clarithromycin, but in general demonstrated less activity than erythromycin, clarithromycin, or azithromycin against a majority of microorganisms. The pharmacokinetic profile of dirithromycin offers the advantages of once-daily dosing and high and prolonged tissue concentrations; dosing adjustments are not needed in the elderly or in patients with renal or mild hepatic impairment. Clinical efficacy and bacteriologic eradication rates with dirithromycin and erythromycin are comparable for the treatment of respiratory and skin and soft tissue infections due to susceptible pathogens. Dirithromycin appears to have adverse effect profiles similar to those of the other macrolides, with reported problems most often related to the gastrointestinal tract. Dirithromycin does not seem to cause clinically important interactions with drugs such as theophylline, oral contraceptives, cyclosporine, or terfenadine. CONCLUSIONS: Dirithromycin offers some attractive pharmacokinetic properties. The long elimination half-life of dirithromycin allows once-daily dosing and higher and more prolonged tissue concentrations than are achievable with erythromycin. The spectrum of activity, adverse effect profile, clinical efficacy, and bacteriologic eradication rate of dirithromycin may be similar to those of erythromycin. No significant drug interactions with dirithromycin have been reported. Based on available data, dirithromycin may not offer any unique clinical advantage over clarithromycin or azithromycin. Future clinical trials may reveal a special role for dirithromycin in patient care.

Anti-Bacterial Agents↗