Linezolid is a novel oxazolidinone antibiotic that has a spectrum of activity encompassing a variety of Gram-positive bacteria. The objectives of this study were twofold: (1) to compare the absorption of linezolid tablets given immediately following a high-fat meal with the absorption of tablets administered while fasting, and (2) to assess the bioavailability of a 375-mg oral dose given while fasting relative to a 375-mg dose of linezolid sterile solution given intravenously. Venous blood samples were taken over the 48 h following the single dose administration of both the oral and intravenous (IV) treatment. Samples were subsequently frozen for the determination of linezolid concentrations by HPLC. The only statistically significant difference between the fasted and the fed treatment was in peak plasma concentration, with the mean C(max) for fasted subjects being 23% greater than that for subjects after consumption of a high-fat meal. Comparable AUC(0-infinity) values were measured under both conditions, indicating that the overall extent of absorption is the same. Therefore, the difference in C(max), while statistically significant, should not affect the therapeutic efficacy of linezolid when it is administered with food. There were no statistically significant differences in AUC(0-infinity), CL or half-life between the fasted oral treatment and the intravenous treatment. As expected, C(max) was statistically different between the two treatments. However, the mean absolute bioavailability (F) of the tablet, using the IV sterile solution as the reference treatment, was 103% (+/-20%).

Verapamil modestly inhibited almotriptan clearance to a degree consistent with the modest contribution of CYP3A4 to almotriptan metabolism. This observation and the lack of effect of verapamil on the tolerability to almotriptan administration suggest that no reduction of the almotriptan dose is warranted.

The memory effects of adinazolam were assessed using the computerized neuropsychological test battery (CNTB). In a single-blind crossover study, 12 volunteers received 2 x 20 mg adinazolam mesylate immediate-release (CT) tablets, 2 x 30 mg sustained-release (SR) tablets, and placebo. Plasma adinazolam and N-desmethyladinozolam (NDMAD) were determined by high-pressure liquid chromatography. Choice reaction time and word-list-learning/delayed-recall CNTB modules were administered at 0, 1, 3 and 6 hours after dosing. Adinazolam and NDMAD maximum peak plasma concentration were lower after SR tablets. Immediate-release tablets significantly prolonged reaction time compared with placebo and SR tablets; reaction time after SR tablets did not differ from placebo. Differences between SR and CT tablets in memory were significant only at 1 hour, but memory scores tended to be higher after SR tablet administration than after the CT tablet. At all times, memory scores were significantly lower than placebo for active treatments. Results suggest that memory is more impaired at lower NDMAD concentrations than is psychomotor function.