M Perez-Reyes — Page 4

PubMedDate not supplied

Naltrexone disposition in man after subcutaneous administration.

The metabolism, excretion, and pharmacokinetics of [15,16-3H2]naltrexone were studied in six human males after sc administration of the hydrochloride salt. Biological fluids were analyzed by a combination of high performance liquid chromatography with liquid scintillation measurement of radioactivity. After administration, naltrexone was rapidly absorbed into the systemic circulation. The mean absorption rate constant was 0.091 +/- 0.008 min-1 (half-life of 7.6 min). In general the metabolic, excretory, and pharmacokinetic patterns for naltrexone were similar to those observed after iv administration of naltrexone to man. The terminal phase plasma rate constant was 0.413 +/- 0.035 hr-1 (half-life of 1.68 hr) for parent drug and 0.0786 +/- 0.0090 hr-1 (half-life of 8.8 hr) for the major metabolite, 6 beta-naltrexone. An average of 76 +/- 6% (+/- SD) of the total radioactivity was recovered in the urine within 72 hr after administration. Naltrexone was found in the urine in both the free (3.4 +/- 0.8% of dose) and conjugated (6.8 +/- 2.1% of dose) form. 6 beta-Naltrexol was present in urine largely in the unconjugated form (28 +/- 7% of dose) but the conjugated form was also found (12 +/- 3% of dose).

Administration, Oral↗

PubMedDate not supplied

Pharmacokinetics of methamphetamine self-administered to human subjects by smoking S-(+)-methamphetamine hydrochloride.

S-(+)-methamphetamine hydrochloride ("ice") is abused by smoking (inhaling the vapors of the material). Male human volunteers inhaled the drug from a pipe heated at 300 degrees-305 degrees C for an average inhaled dose of 21.8 +/- 0.3 (SE) mg. The same volunteers were given an intravenous injection of 15.5 mg of S-(+)-methamphetamine hydrochloride. Methamphetamine and its metabolite amphetamine were analyzed in plasma, saliva, and urine by gas chromatography. The bioavailability of smoked methamphetamine was 90.3 +/- 10.4%. (Oral bioavailability calculated from this study and a previous one was 67.2 +/- 3.1%). The geometric mean plasma half-life was 11.1 hr for smoked methamphetamine and 12.2 hr for the intravenous drug. These values agreed with urinary excretion rate data. The volume of distribution in the elimination phase was 3.24 +/- 0.36 liter/kg for the smoked dose and 3.73 +/- 0.59 liter/kg for the intravenous dose. The mean residence times were 11.5 +/- 0.5 hr and 11.3 +/- 1.74 hr for the two routes. Metabolic clearance represented 58 and 55%, respectively, of the total clearance. Significant amounts of the drug (37-45% of the nominal dose) were excreted in urine as methamphetamine and lesser amounts (7% of the nominal molar dose) as amphetamine. Renal clearance was equivalent for the two routes. Methamphetamine concentrations in plasma after inhalation showed a plateau. A model involving both a fast and a slow input function fit the data from 4 of the 6 subjects and indicated a terminal elimination rate that agreed with results from model-independent pharmacokinetic calculations. The drug caused significant subjective and cardiovascular effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗