ABSTRACT Multiple in vivo studies have characterized the pharmacodynamics of drugs from the triazole and polyene antifungal drug classes. Fewer studies have investigated these pharmacodynamic relationships for the echinocandin drug class. We used a neutropenic murine model of disseminated Candida albicans , Candida tropicalis , and Candida glabrata infection to characterize the time course of activity of the new echinocandin anidulafungin. The pharmacokinetic-pharmacodynamic (PK-PD) indices (the percentage of time that the drug concentration was above the MIC, the ratio of the area under the concentration-time curve from 0 to 24 h [AUC 0-24 ] to the MIC, and the ratio of the maximum serum drug concentration [ C max ] to the MIC) were correlated with in vivo efficacy, as measured by organism numbers in kidney cultures after 96 h of therapy. The kinetics following intraperitoneal anidulafungin dosing in neutropenic infected mice were monitored. Peak levels and AUCs were linear over the 16-fold dose range studied. The drug elimination half-life in serum ranged from 14 to 24 h. Single-dose postantifungal-effect studies demonstrated prolonged suppression of organism regrowth after serum anidulafungin levels had fallen below the MIC. Of the four dosing intervals studied, treatment with the more widely spaced dosing regimens was most efficacious, suggesting the C max /MIC ratio as the PK-PD index most predictive of efficacy. Nonlinear regression analysis suggested that both the C max /MIC and AUC/MIC ratios were strongly predictive of treatment success. Studies were then conducted with 13 additional C. albicans , C. tropicalis , and C. glabrata isolates with various anidulafungin susceptibilities (MICs of anidulafungin for these strains, 0.015 to 2.0 μg/ml) to determine if similar C max /MIC and AUC 0-24 /MIC ratios for these isolates were associated with efficacy. The anidulafungin exposures associated with efficacy were similar among Candida species.

Journal Article Compatibility of ondansetron hydrochloride with fluconazole, ceftazidime, aztreonam, and cefazolin sodium under simulated Y-site conditions Get access John A. Bosso, Pharm.D., John A. Bosso, Pharm.D. Professor and Vice Chair for Research College of Pharmacy, Medical Unisersity of South Ciarolina, Charleston, SC Search for other works by this author on: Oxford Academic Google Scholar Randall A. Prince, Pharm.D., Randall A. Prince, Pharm.D. Professor University of Houston, Houston, TX Search for other works by this author on: Oxford Academic Google Scholar Janet L. Fox, Pharm.D. Janet L. Fox, Pharm.D. Assistant Director Clinical Applications, Glaxo Inc., Research Triangle Park, NC Search for other works by this author on: Oxford Academic Google Scholar American Journal of Hospital Pharmacy, Volume 51, Issue 3, 1 February 1994, Pages 389–391, https://doi.org/10.1093/ajhp/51.3.389 Published: 01 February 1994

The stability of ondansetron hydrochloride in 5% dextrose injection and in 0.9% sodium chloride injection when stored frozen, refrigerated, and at room temperature was studied.Solutions of ondansetron 0.03 and 0.3 mg/mL (as the hydrochloride salt) were prepared by adding 1.5 or 15 mg of the drug to 50-mL minibags containing 5% dextrose injection or 0.9% sodium chloride injection. All solutions were prepared in triplicate, and each container was tested in duplicate. Testing at the time of preparation and at each subsequent test interval included visual inspection of color and clarity, determination of pH, and a stability-indicating high-performance liquid chromatographic assay to measure the ondansetron concentration. Conditions assessed included storage at -20-degrees-C for two weeks to three months, 5-degrees-C for 7-14 days, approximately 25-degrees-C for up to 48 hours, and various combinations of these conditions.The concentration of ondansetron in each solution remained above 90% of the original concentration at each observation time under all storage conditions. No changes in color or clarity were observed, and there were only minor changes in pH.Ondansetron 0.03 and 0.3 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection was stable when stored (1) for up to three months at -20-degrees-C, followed by up to 14 days at 5-degrees-C and by 48 hours at 25-degrees-C and (2) for up to 14 days at 5-degrees-C, followed by up to 48 hours at 25-degrees-C.

A naerobic bacteria are becoming increasingly recognized as causes of infection in man. These organisms may act alone or synergistically with aerobic bacteria, either by altering the growth conditions of the 2nd bacterium or by inhibiting antimicrobial action.' Anaerobes are known to cause infections of the head and neck, respiratory tract, gastrointestinal tract, female genital tract, and skin and soft tissues.' In addition, a number of newer clinical syndromes, such as Clostridium difficile colitis, have recently been described. The character of anaerobic pathogens is also changing. No longer can the clinician assume that anaerobic infections occurring "above the diaphragm" will be amenable to penicillin therapy.3 Moreover, the pathogenicity of anaerobes with varying antibiotic susceptibility patterns, which were once thought to be nonpath-ogenic (i.e., the Bacteroidesfragilis group), is becoming more evident.' Therapy for anaerobic or mixed anaerobic and aerobic infections is no longer as straight-forward as it once appeared. This article reviews the antibacterial and pharmacologic characteristics of 4 anti-anaerobic" antibiotics-cefoxitin, cefotetan, clindamycin, and metronidazole-and discusses their clinical indications.

To assess fever-induced changes in theophylline pharmacokinetics in the rabbit model, six healthy, male, New Zealand white rabbits were studied using a randomized, matched-pair design. In treatment 1, 15 mg/kg of theophylline was infused into the left marginal ear vein, and several blood samples were collected from the opposite ear for 10 hours. Treatment 2 was conducted in an identical manner, except 20 to 40 micrograms/kg of Escherichia coli endotoxin was injected into the left marginal ear vein to induce fever. The majority of the rabbits had slight decreases in the slowest disposition rate constant and increases in the volume of distribution at steady state; however, total body clearance was only minimally (5%) changed. No statistically significant differences were noted between these values (Hotelling T2 = 0.32). Given the sample and methods, fever apparently does not affect theophylline pharmacokinetics.

The objective of this study was to quantitate cefotaxime and its active metabolite, desacetyl cefotaxime, in the distal airways and to compare these levels to concentrations in plasma. Respiratory secretions were obtained from the subsegmental level in 17 adult patients undergoing fiber-optic bronchoscopy within 2 h after receiving four doses of cefotaxime (2 g intravenously every 6 h). In 11 patients, cefotaxime levels measured by high-pressure liquid chromatography in bronchial secretions were below detectable limits (less than 0.5 mg/liter); however, levels of desacetyl cefotaxime exceeded 1.5 mg/liter in 9 of these 11 patients (range, 1.6 to 10 mg/liter). Concentrations of desacetyl cefotaxime in lung secretions (6.9 +/- 0.85 [standard error] mg/liter) was 77% of mean levels of desacetyl cefotaxime in plasma (8.9 +/- 1.26 mg/liter). In summary, concentrations of desacetyl cefotaxime in bronchial secretions are markedly higher than those of cefotaxime.

No AccessJournal of Urology1 Oct 1982Metronidazole A. Molavi, J.L. Lefrock, and R.A. Prince A. MolaviA. Molavi More articles by this author , J.L. LefrockJ.L. Lefrock More articles by this author , and R.A. PrinceR.A. Prince More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(17)53232-2AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "Metronidazole." The Journal of Urology, 128(4), p. 874 © 1982 by The American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 128Issue 4October 1982Page: 874 Advertisement Copyright & Permissions© 1982 by The American Urological Association Education and Research, Inc.MetricsAuthor Information A. Molavi More articles by this author J.L. Lefrock More articles by this author R.A. Prince More articles by this author Expand All Advertisement PDF downloadLoading ...

The effect of tetracycline hydrochloride on theophylline kinetics was studied. Eight nonsmoking men received a 15-minute infusion of theophylline (aminophylline) 5 mg/kg before (control) and after (experimental) a seven-day tetracycline course of 1 g daily. Each subject acted as his own control. Multiple serum samples were collected for 24 hours after each dose and were analyzed for theophylline by enzyme immunoassay. At each phase of study the mean +/- S.D. pharmacokinetic values were as follows: apparent volume of distribution (liter/kg), 0.44 +/- 0.05 (control) and 0.42 +/- 0.04 (experimental); clearance (ml . min/kg) 0.82 +/- 0.15 (control) and 0.73 +/- 0.07, (experimental); and elimination half-life (hours), 6.27 +/- 1.08 (control) and 6.72 +/- 0.78 (experimental). Tetracycline did not significantly alter the kinetics of theophylline. The probability of missing a 25% change in the kinetic values (Type II error) was less than 6%. Patients receiving theophylline do not appear to be at added risk for the development of toxicity as a result of a kinetic interaction when tetracycline hydrochloride is added to the therapeutic regimen.

The complex physiology of the blood-brain barrier and the characteristics of an antimicrobial which govern its distribution into the brain are poorly understood. Likewise, available data regarding CSF antimicrobial concentrations after extra-CNS administration, as tabulated in this review, are inadequate. Because of the potentially dire consequences that result from inappropriately treated CNS infections, large cooperative studies using standardized methodology are needed. Suggestions for such methods are outlined.

The case of a 69-year-old woman with procainamide-induced agranulocytosis is reported, and literature reports of 14 other such cases are reviewed. The patients was exposed to procainamide, prescribed for atrial fibrillation, for 26 days, with a daily dose of 1.5 to 4 g and a total dose of 57.5 g. She recovered from agranulocytosis after discontinuation of the drug and hospital treatment for 16 days. Among the reported cases of procainamide-induced agranulocytosis, the daily dosage ranged from 750 mg to 4.5 g; the total ingested dose before agranulocytosis was observed ranged from 36.5 to 316.3 g. Patients treated with procainamide should be instructed to report any soreness of the mouth, throat or gums; unexplained fever; or any symptoms of upper respiratory tract infection. If white blood cell counts indicate bone marrow depression, the drug should be withdrawn and appropriate evaluation begun at once.

Two case reports of patients who developed a toxic neuropathy associated with nitrofurantoin are presented. In each case the patient had normal renal function and the symptoms abated upon withdrawal of the drug. Although the specific mechanism by which nitrofurantoin causes the neuropathy is still not known, various hypotheses are discussed and the literature is reviewed. The danger of nitrofurantoin administration in patients with impaired renal function is emphasized, and it is stress that early signs and symptoms of peripheral neuropathy be reported and the drug immediately discontinued. Even in the presence of normal renal function, the recommended dosage and duration of therapy should not be exceeded.