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Biomedical subjects

S C Piscitelli

Publications and source records attributed to S C Piscitelli.

At least 73 records · Page 4Linked to original sources
PubMed1994

Steady-state pharmacokinetics of cefoperazone and sulbactam in patients with acute appendicitis.

OBJECTIVE: To determine the steady-state pharmacokinetics of intravenously administered cefoperazone and sulbactam when given in combination to patients with acute appendicitis. METHODS: Six patients with normal renal and hepatic function received cefoperazone 2 g with sulbactam 1 g prior to appendectomy and then every 12 hours. Serial blood samples were collected after each patient received at least three doses of cefoperazone/sulbactam. RESULTS: Cefoperazone and sulbactam could be best described by a two-compartment model. Mean +/- SD values for cefoperazone steady-state volume of distribution (Vssd), elimination half-life (t1/2 beta), clearance (Cl), and area under the curve (AUC0-t) were 19.8 +/- 8.0 L, 3.97 +/- 1.06 h, 62.6 +/- 16.3 mL/min, and 556.9 +/- 122.0 mg.h/L, respectively. Sulbactam Vssd, t1/2 beta, Cl, and AUC0-t were 34.7 +/- 13.9 L, 1.39 +/- 0.4 h, 288.6 +/- 68.2 mL/min, and 64.8 +/- 24.5 mg.h/L, respectively. CONCLUSIONS: Compared with data from healthy volunteers, cefoperazone exhibited a decreased Cl and increased Vssd and t1/2 beta in patients with acute appendicitis. An increased Vssd also was observed for sulbactam. The disposition of cefoperazone/sulbactam is altered in this group of patients; however, these changes are not likely to warrant a dosage reduction.

Acute Disease↗
PubMed1994

Oral antibiotic usage in hospitalized patients.

With the introduction of the fluoroquinolones, oral antibiotic usage is becoming an increasingly important issue. The medical record of 119 patients receiving oral antibiotics at a university hospital were reviewed to examine demographics and patterns of usage. The population was predominantly female and below 50 years of age. Urinary tract infections were most common followed by infections of the respiratory tract and skin and skin structure. The majority of usage was empiric in nature. The most commonly prescribed antibiotics were trimethoprim/sulfamethoxazole, cephalexin, and ampicillin/amoxicillin. Monotherapy with an oral agent was observed in 82% of the cases. Intravenous antibiotics were administered prior to oral therapy in 61% of the patients studied. The authors observed a trend from combination intravenous therapy to single-agent oral therapy. Of the patients discharged on an oral antibiotic, 84% received a prescription for the agent originally prescribed for them in the hospital. Tracking of oral antibiotic inpatient use is effective at assessing major trends in usage.

Administration, Oral↗
PubMed1994

Plasma clozapine and haloperidol concentrations in adolescents with childhood-onset schizophrenia: association with response.

BACKGROUND: Plasma clozapine and haloperidol concentrations were studied in adolescents being treated for childhood-onset schizophrenia. METHOD: Eleven patients (9 boys, 2 girls; mean age = 14.1 +/- 2.1 years) received a 6-week blinded or open trial of clozapine. Five patients also received 6 weeks of blinded or open haloperidol. Doses were increased on an individual basis to a mean 6-week dose of 5.99 +/- 2.6 mg/kg/day for clozapine and 0.24 +/- 0.20 mg/kg/day for haloperidol. The Brief Psychiatric Rating Scale and Bunney Hamburg Rating Scale were completed weekly for each subject. Weekly blood samples were obtained during therapy and assayed by high performance liquid chromatography. RESULTS: The mean clozapine level at Week 6 was 378.3 ng/mL and ranged from 77.5 to 1050 ng/mL. The mean Week 6 haloperidol level was 23.0 ng/mL (range, 6.2-44.3 ng/mL). The clozapine desmethyl and N-oxide metabolites achieved mean concentrations of 77% and 18%, respectively, of those of the parent compound. The mean ratio of haloperidol/reduced haloperidol was 4.48 (range, 0.76-8.76). Clozapine concentrations versus clinical benefit exhibited a consistent linear relationship among patients (correlation range, 0.26-0.96). Conversely, poor and inconsistent correlations between haloperidol concentrations and clinical effects were observed. No relationships were noted between clozapine or haloperidol dose and clinical effects. CONCLUSION: Adolescents with schizophrenia produce a greater amount of desmethylclozapine than previously seen in adults. Plasma clozapine concentrations appear to be related in a linear fashion to clinical improvement.

Adolescent↗
PubMed1993

The disposition of doxorubicin on repeated dosing.

Twelve cancer patients (aged 49-74 years) receiving doxorubicin (66 +/- 8 mg/m2) as a 1-hour intravenous infusion had serial serum samples (0-48 hours) obtained after the first and second courses of therapy. Mean number of days between courses was 24.3, and all patients had normal liver function. Patients received the same concomitant antineoplastic agents and doses in both courses. Doxorubicin and doxorubicinol concentrations were assayed by high-performance liquid chromatography and fitted to a two- or three-compartment infusion model. White blood cell and platelet toxicity were evaluated as (initial--nadir/initial)* 100. Differences in pharmacokinetic parameters were determined by a paired t test. Wide intrapatient and interpatient variability was seen between therapeutic courses. A significant decrease in the apparent volume of distribution of the central compartment (Vc = 16.6 versus 10.4 L/m2; P < .05), and a nonsignificant decrease in clearance (CL = 748 versus 658 mL/min/m2) was observed on the second course of therapy. Doxorubicinol area under the curve and elimination half-life were similar between courses. Extensive chemotherapy-induced changes in white blood cell and platelet counts were observed but were similar in degree for courses 1 and 2. These data suggest that higher initial doxorubicin concentrations on the second course of therapy are secondary to an alteration in distribution volume (Vc). In this subset of patients, however, these changes were not associated with an increase in hematologic toxicity.

Aged↗
PubMed1993

Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small cell lung cancer.

The pharmacokinetics and pharmacodynamics of doxorubicin and its metabolite, doxorubicinol, were studied in 35 adult (mean age, 66 1/2 years) patients with small lung cell cancer after a 1-hour intravenous infusion at a dose ranging from 45 to 72 mg/m2. All patients also received concomitant therapy with cyclophosphamide and vincristine. Serum concentrations were sampled to 48 hours after dosing. Wide interpatient variability was observed for all pharmacokinetic parameters with coefficients of variation for apparent volume of distribution, clearance, and area under the curve (AUC) of 62%, 65%, and 65%, respectively. Four patients with impaired liver function showed a significant (p < 0.05) decrease in clearance (239 versus 666 ml/min/m2) and increases in AUC (4610 versus 1834 ng.hr/ml) and elimination half-life (49.3 versus 25.6 hours) compared with patients with normal hepatic function. A significant relationship was found between systemic exposure of doxorubicin (defined by AUC) and surviving factor of white blood cells (r = 0.57, p = 0.0025). No relationships were noted between doxorubicinol exposure and surviving factor of white blood cells or platelets. These findings show the important relationship between systemic exposure of doxorubicin and the degree of myelosuppression in patients with small cell lung cancer.

Aged↗
PubMed1993

New oral macrolide and fluoroquinolone antibiotics: an overview of pharmacokinetics, interactions, and safety.

During the past decade, there has been a resurgence of interest in the development of oral macrolide and fluoroquinolone antimicrobial agents. Azithromycin and clarithromycin are two new oral macrolides whose pharmacokinetics (compared with those of erythromycin) are characterized by improved oral bioavailability, increased tissue penetration and persistence, and longer elimination half-lives. A limited number of interactions with other drugs have been reported for azithromycin and clarithromycin. The most common adverse reactions to the new macrolide agents include nausea, diarrhea, and abdominal pain. Norfloxacin, ciprofloxacin, ofloxacin, temafloxacin, and lomefloxacin are the oral fluoroquinolones that have been marketed in the United States thus far. In comparison to nalidixic acid, the newer fluoroquinolones have improved pharmacokinetic properties, including greater oral absorption, increased peak serum concentrations and areas under the curve, higher tissue concentrations, and longer elimination half-lives. Divalent or trivalent cations can alter the absorption of all fluoroquinolones. Some of the fluoroquinolones (norfloxacin, ciprofloxacin, and ofloxacin) can inhibit the cytochrome P-450 enzyme system and thereby cause increased serum concentrations of drugs like theophylline and caffeine. Adverse reactions to the fluoroquinolones primarily involve the gastrointestinal system, skin, and central nervous system.

Administration, Oral↗
PubMed1993

Effectiveness of a dapsone compliance program in leprosy.

BACKGROUND: Long-term effectiveness of a dapsone compliance program was assessed in patients with leprosy. METHODS: The monitoring program consists of urine dapsone/creatinine ratio determination at each visit with subsequent patient feedback and education. Eighty-eight patients receiving dapsone and seen in a leprosy clinic from 1985-1990 were included. RESULTS: The proportion of patients compliant with dapsone during a given year ranged from 70.0% (1987) to 94.4% (1989). Overall compliance for the 6-year period was 81.6%. This level of compliance was significantly different (P < 0.05) than the baseline compliance in the leprosy clinic of 46.7%. CONCLUSIONS: Compliance monitoring, combined with active patient involvement, was effective in sustaining high compliance over a 6-year period.

Adult↗
PubMed1993

Therapeutic monitoring and pharmacist intervention in a Hansen's disease clinic.

OBJECTIVE: To describe the role of the clinical pharmacist in a Hansen's disease (HD, leprosy) clinic and to describe the development, validation, and operation of a dapsone compliance monitoring program. RATIONALE: HD remains a major, worldwide healthcare problem. Dapsone is the drug of choice for treatment of HD; however, high rates of noncompliance with this agent have been reported by many treatment centers. The assessment of compliance in HD patients is important to help distinguish between treatment failure secondary to noncompliance or to the development of resistance. SETTING: In the US, the Chicago Regional Hansen's Disease Center at the University of Illinois at Chicago is one of ten centers that provide comprehensive care to patients diagnosed with this condition. This article reviews the clinical pharmacy services and dapsone compliance program in the clinic encompassing the years 1983-93. RESULTS: The clinical pharmacist provides a variety of clinical services in the clinic as well as coordinating the clinical research program. A pharmacist-generated dapsone compliance program led to improvement in compliance rates and clinical outcome. This improvement in compliance has been sustained over an extended period of time. CONCLUSIONS: The clinical pharmacy services performed in the HD clinic provide a model for pharmacy involvement in other chronic disease states. The dapsone compliance program has been successful in improving patient care and obtaining reimbursement for clinical pharmacy services.

Academic Medical Centers↗
PubMed1992

Streptococcus milleri group: renewed interest in an elusive pathogen.

The following review examines the bacteriological characteristics, epidemiology, pathogenicity and antimicrobial susceptibility of the "Streptococcus milleri group". "Streptococcus milleri group" is a term for a large group of streptococci which includes Streptococcus intermedius, Streptococcus constellatus and Streptococcus anginosus. Usually considered commensals, these organisms are often associated with various pyogenic infections including cardiac, abdominal, skin and central nervous system infections. Organisms of the "Streptococcus milleri group" are often unrecognized pathogens due to the lack of uniformity in classifications and difficulties in microbiological identification. Penicillin G, cephalosporins, clindamycin and vancomycin all possess activity against these streptococci. Use of agents with poor activity may promote infections with "Streptococcus milleri group" and allow it to exhibit its pathogenicity. An understanding of these organisms may aid in their recognition and proper treatment.

Animals↗
PubMed1992

Clinical pharmacokinetics of metronidazole and other nitroimidazole anti-infectives.

Metronidazole was first introduced for the treatment of trichomoniasis. Its therapeutic use has subsequently been expanded to include amoebiasis, giardiasis and, more recently, anaerobic infections. Most of the early pharmacokinetic studies employed nonspecific assays such as microbiological and chemical assays. These assays were not able to differentiate the parent drug from the metabolites or other interfering substances. Pharmacokinetic data obtained through the use of specific chromatographic techniques provide the basis for this review of recent pharmacokinetic findings concerning metronidazole and other nitroimidazole antibiotics. When given intravenously or orally at usual recommended doses, metronidazole attains concentrations well above the minimum inhibitory concentrations for most susceptible micro-organisms. The drug has an oral bioavailability approaching 100%. Rectal and vaginal administration results in a smaller amount of drug absorption and lower serum concentrations. Metronidazole has limited plasma protein binding but can attain very favourable tissue distribution, including into the central nervous system. The drug is extensively metabolised by the liver to form 2 primary oxidative metabolites: the hydroxy and acetic acid metabolites. The kidney is responsible for the elimination of only a small amount of the parent drug; however, normal excretion of the 2 metabolites is dependent on the integrity of kidney function. The metabolism of metronidazole was found to vary among patient groups. Preterm and term infants have lower total body clearance (CL) and prolonged elimination half-lives. However, children older than 4 years old were observed to have pharmacokinetic parameters similar to those in adults. Reduced CL was also observed in children who are malnourished. Elderly patients have reduced renal excretion of both the parent drug and hydroxy metabolite. Pharmacokinetic parameters in pregnant patients were not significantly different from those in nonpregnant women; however, the drug is distributed into breastmilk and the infant will be exposed to the drug through the nursing mother. Patients undergoing gastrointestinal surgery or having enteric diseases and those who are hospitalised or critically ill also have altered pharmacokinetics. Metabolism of the drug is reduced in patients with liver dysfunction, giving delayed production of metabolites. In contrast, renal failure has little effect on the elimination of the parent drug, but affects the excretion of the metabolites more significantly. Haemodialysis was found to remove a substantial amount of the metronidazole while the effect of peritoneal dialysis was more limited. Energy and protein deficient diets as well as occupational exposure to gasoline did not alter metronidazole pharmacokinetics. However, the effect of alcohol consumption on metronidazole CL requires further study.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1992

Clarithromycin and azithromycin: new macrolide antibiotics.

The chemistry, mechanism of action, antimicrobial spectrum, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of clarithromycin and azithromycin are described. Clarithromycin and azithromycin are new macrolide antibiotics that are similar in structure to erythromycin. Compared with erythromycin, clarithromycin demonstrates increased activity against Staphylococcus aureus, streptococci, Legionella pneumophila, Moraxella catarrhalis, and Chlamydia trachomatis. Clarithromycin also has in vitro activity against Mycobacterium avium complex (MAC) and Toxoplasma gondii. Azithromycin has increased gram-negative activity compared with erythromycin, including activity against Haemophilus influenzae, while maintaining activity against gram-positive organisms. Azithromycin also has activity against sexually transmitted organisms including Chlamydia trachomatis. The pharmacokinetic profiles of clarithromycin and azithromycin are characterized by good oral bioavailability, excellent tissue penetration and persistence, and long elimination half-lives, which allow for once-daily or twice-daily dosing. Initial data show that clarithromycin and azithromycin are effective for the treatment of upper-respiratory-tract and lower-respiratory-tract infections and infections of the skin and skin structures. Azithromycin has been shown to be effective for the treatment of sexually transmitted diseases caused by Chlamydia trachomatis. Clarithromycin and azithromycin have been used to treat MAC and Toxoplasma infections in patients with the acquired immunodeficiency syndrome. The most frequently reported adverse effects for both agents have been nausea, diarrhea, and abdominal pain. Oral formulations of clarithromycin and azithromycin have recently been approved by the FDA. Clarithromycin and azithromycin are new macrolide antibiotics that have potential advantages over erythromycin; however, the role of these agents will be better defined as results of more ongoing trials become available for evaluation.

Azithromycin↗
PubMed1991

Effects of ranitidine and sucralfate on ketoconazole bioavailability.

Ketoconazole is an oral imidazole antifungal agent useful in the treatment of opportunistic fungal infections. Gastrointestinal absorption of this agent is variable and dependent on the presence of gastric acid. This study compared the effects of concomitant sucralfate administration with ranitidine administration on the pharmacokinetic disposition of a 400-mg ketoconazole dose. Six healthy male volunteers were randomized to receive 400 mg of ketoconazole alone, 1.0 g of sucralfate concomitantly with a 400-mg ketoconazole dose, or ranitidine, administered 2 h prior to a 400-mg ketoconazole dose to titrate to a gastric pH of 6. All subjects received all three regimens in crossover fashion. Gastric pH was measured continuously for 4 h after ketoconazole administration in all subjects by using a Heidelberg radiotelemetry pH capsule. Relative ketoconazole bioavailability was compared between treatments. With sucralfate, five of six subjects demonstrated a decrease in the peak drug concentration in serum as well as an increase in the time to peak concentration, indicating a delay in ketoconazole absorption. The mean area under the concentration-time curve from 0 to 12 h for ketoconazole following gastric alkalinization was significantly different from that of either ketoconazole alone or ketoconazole with sucralfate (P less than 0.01). Continuous gastric pH monitoring allowed correlation between the decrease in ketoconazole bioavailability observed with ranitidine and the increase in gastric pH. The apparent decrease in ketoconazole bioavailability observed with sucralfate appears to be caused by an alternative mechanism since a change in gastric pH was not observed. On the basis of these findings, separating the administration of ketoconazole and sucralfate should be considered to decrease the potential for interaction of sucralfate on ketoconazole bioavailability.

Adult↗
PubMed1990

Fluconazole: a new triazole antifungal agent.

Fluconazole is a fluorine-substituted, bis-triazole antifungal agent. Its mechanism of action, like that of other azoles, involves interruption of the conversion of lanosterol to ergosterol via binding to fungal cytochrome P-450 and subsequent disruption of fungal membranes. Activity against Aspergillus spp., Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Cryptococcus neoformans, Histoplasma capsulatum, and Paracoccidioides brasiliensis has been demonstrated in several animal models. Fluconazole can be administered both orally and intravenously. Mean peak serum concentrations achieved in human volunteers after 50 and 100 mg (oral) are 3.1 and 7.0 mumols/L respectively. Protein binding is low (11 percent) and cerebrospinal fluid to serum ratio is 0.58 to 0.89. Serum half-life is long (22-32 hours) and elimination is via renal clearance of unchanged drug. Clinical trials and reports support the use of fluconazole in treatment of candidiasis, particularly oropharyngeal and esophageal infections in immunocompromised hosts. Fluconazole is also approved for initial and suppressive therapy of cryptococcal meningitis. Its role in management of systemic fungal infections will be further defined once results of other comparative trials become available. Fluconazole is well tolerated and its effects on steroidogenesis are markedly less than those of ketoconazole. Antipyrine clearance is not altered at low doses (50 mg) of fluconazole; however, drug interactions with the use of larger doses can be anticipated with agents such as cyclosporin, phenytoin, oral hypoglycemics, and warfarin. Rifampin appears to decrease metabolic clearance of fluconazole. Fluconazole is available as oral and parenteral formulations. Once-daily doses of 100-400 mg are recommended. Dosage reduction is advised for patients with impaired renal function.

Animals↗
PubMedDate not supplied

Lipid formulations of amphotericin B: clinical perspectives for the management of invasive fungal infections in children with cancer.

During the past four decades, amphotericin B deoxycholate has been the cornerstone of systemic chemotherapy for life-threatening fungal infections. Despite a broad spectrum of antifungal activity, its utility is greatly hampered by renal toxicity and limited clinical efficacy, in particular in patients with profound and persistent neutropenia. The novel lipid formulations of amphotericin B have distinct physicochemical properties resulting in different distribution patterns. Nevertheless, they all share a considerable reduction of nephrotoxicity, which allows for the delivery of higher daily dosages of amphotericin B. Preliminary efficacy data indicate that these compounds are overall at least as effective as amphotericin B deoxycholate. However, information for children is limited, and comparative studies for their use as first line agents are only in their beginnings. In this article, we review the clinical pharmacokinetics, safety, and efficacy of the lipid formulations of amphotericin B with special emphasis on pediatric data, and we seek to provide a rational framework for the determination of their current role in patients with cancer and proven or suspected invasive fungal infections.

Amphotericin B↗
PubMedDate not supplied

Development of resistance during antimicrobial therapy: a review of antibiotic classes and patient characteristics in 173 studies.

The incidence of emergent resistance and clinical factors affecting its development were evaluated by retrospective review of 173 studies encompassing over 14,000 patients. Eight antibiotic classes and 225 individual treatment regimens were evaluated. Emergent resistance occurred among 4.0% of all organisms and 5.6% of all infections treated. It appeared to be significantly more frequent with penicillin and aminoglycoside monotherapy, with significantly lower rates associated with imipenem-cilastatin, aztreonam, and combination therapy. Clinical failure also appeared to be significantly more likely to occur after emergence of resistance among organisms treated with fluoroquinolones or aminoglycosides. Infections associated with higher resistance rates were cystic fibrosis, osteomyelitis, and lower respiratory tract infections. Resistance was most common in patients in intensive care units or receiving mechanical ventilation. It was also significantly frequent among studies performed in university or teaching hospitals. Organisms associated with high resistance rates were Pseudomonas aeruginosa, Serratia, Enterobacter, and Acinetobacter sp. Factors such as infection type, underlying diseases, type of institution, and specific pathogens warrant consideration when examining emergent resistance.

Aminoglycosides↗
PubMedDate not supplied

Candidal urinary tract infections: a comprehensive review of their diagnosis and management.

Despite its prevalence, the significance of candiduria remains uncertain. The pathogenesis of candidal urinary tract infections has been relatively well characterized and many risk factors have been identified. The disorders lack consistent diagnostic criteria, however, such as the presence of pyuria or a colony count above which is predicative of presence, location, or severity of infection. Treatment is unclear due to lack of data defining the natural progression of the disease. Although often recommended, it may not always be possible to remove risk factors. Amphotericin B, fluconazole, 5-flucytosine, and other antifungal agents are important agents for managing candidal urinary tract infections.

Antifungal Agents↗