Oral DFMO at the dose of 125 mg/kg body weight given every 6 h for 14 days may not produce adequate therapeutic plasma and CSF levels for patients with late-stage T.b. gambiense sleeping sickness.

The pharmacokinetics of atovaquone and cycloguanil appeared to be influenced by the pregnancy status, resulting in an decrease in the Cmax and AUC of approximately twofold.

The effect of oral controlled-release (CR), oral transmucosal (buccal; TMD) and transdermal (TDD) drug delivery systems on plasma concentrations of melatonin (MT) and its principal metabolite in human subjects using a crossover, single dose design was evaluated. Twelve adult male volunteers participated in the study and received all three dosage forms on three separate occasions. All patch dosage forms were removed after 10 h of wear. Plasma concentrations of the parent drug and its metabolite, 6-sulfatoxymelatonin (MT6s) were measured by radioimmunoassay. Between-subject plasma concentrations of MT were very variable following both oral CR and TDD. Use of the oral CR system gave plasma MT profiles in some subjects that were initially similar to physiological levels, but then differed substantially from physiological in the rate of MT offset; in a few subjects, plasma MT levels remained consistently much below normal nocturnal physiological levels. Also, the ratio of metabolite to parent drug by the oral CR route was many times greater than physiological. TDD resulted in a significant delay in systemic drug levels and a gradual decline in drug delivery after patch removal, possibly due to deposition of melatonin in the skin. TDD failed to simulate the physiological plasma profile of MT (rapid achievement of steady-state blood levels and rapid decline after removal of the patch; i.e., so-called "square-wave" profile). TMD provided prompt systemic drug levels with less variability than oral CR or TDD delivery. Also, plasma MT levels fell promptly and rapidly after removal of the patch. No indication of mucosal deposition was observed. TMD was able to mimic the physiological plasma profiles of both MT and its principal metabolite.

No abstract

This study was undertaken to determine the bioavailabilityof a 1200 mg miconazole nitrate vaginal ovule in 20 healthy premenopausal females following a single application (Day 1, Group 1) and two applications, 48 hours apart (Day 1 and Day 3, Group 2). In Dose Group 1 (n = 10), the mean Cmax of 10.7 ng/ml occurred at 18.4 hours. The average plasma miconazole concentration was calculated to be 5.7 ng/ml during the 4- to 96-hour time interval. In Dose Group 2 (n = 10), mean Cmax values were 10.8 ng/ml and 12.0 ng/ml and occurred at 18.4 hours (Day 1) and 16.0 hours (Day 3), respectively. Comparing AUC0-48 on Days 1 and 3 (338 vs. 408 ng x h/ml) indicated small accumulation of plasma miconazole, while AUC0-48 obtained from Dose Group 2, Day 1 was similar to that of Dose Group 1 (338 vs. 329 ng x h/ml, respectively). Plasma miconazole profiles were best described by a monoexponential equation with zero-order input. Pharmacokinetic simulations performed on the pooled data from two dose groups (n = 20) suggest a steady-state accumulation after five doses administered daily or three doses taken once every other day. Drug exposure was similar to that of the marketed formulation (MONISTAT 7 vaginal cream), applied once daily for 7 days and more than 100-fold less than that reported when given intravenously or orally.