No abstract

The ability of healthy male volunteers to metabolize a 30-mg oral dose of dextromethorphan (DM) was studied in 252 Americans. Two blood samples were collected at four and 24 hours after administration of the dose. The resulting plasma was analyzed for unchanged DM. The volunteers were classified as slow, intermediate, or fast metabolizers on the basis of plasma concentrations of DM. Further differentiation of slow and intermediate metabolizers was achieved by comparing the two-point estimates of elimination-rate constants. In the population studied, 84.3% were fast DM metabolizers, 6.8% were intermediate metabolizers, and 8.8% were slow metabolizers. Previous reports have related the slow DM metabolizers to slow debrisoquin metabolizers, but no such correlations have been achieved with intermediate DM metabolizers. These intermediate DM metabolizers may suggest a new polymorphism not related to debrisoquin or may suggest that "debrisoquin gene" regulation is more complex than originally suggested.

The purpose of this study was to evaluate the multiple dose pharmacokinetics and acute safety of piroxicam and cimetidine alone and in combination in cats. Seven healthy cats were included in this randomized-crossover study. The cats were assigned to groups designated to receive cimetidine alone (15 mg/kg, p.o., q12 h), piroxicam alone (0.3 mg/kg, p.o., q24 h), and piroxicam combined with cimetidine (both at aforementioned doses). The cats were dosed for 10 days followed by at least a 2-week washout period between trials. Serial blood samples were collected following the first and last doses and analyzed utilizing a high-performance liquid chromatography with mass spectrometry detection (LC/MS) assay. Pharmacokinetic parameters were determined using noncompartmental analysis. Endoscopic evaluation of the gastric mucosa was performed and serum urea nitrogen (SUN), creatinine, alkaline phosphatase (ALP), and alanine transaminase (ALT) activities were evaluated. There were not a clinically relevant difference between the pharmacokinetic parameters of piroxicam administered alone or in combination with cimetidine after either the first or last dose. Gastric ulcers were not observed in any cats although gastric erosions were. The SUN, creatinine, ALP, and ALT activities remained within reference ranges for all cats. It appears that once daily, short-term use of piroxicam alone and in combination with cimetidine in cats is relatively safe based on the parameters evaluated in this study. However, further studies are necessary to determine the long-term gastrointestinal safety of piroxicam.

The pharmacokinetics of OddC in rats were linear over the dose range studied.