No abstract

delta-9-Tetrahydrocannabinol (THC) kinetics and dynamics of self-reported psychologic "high" effect are analyzed in six subjects who smoked marijuana cigarettes of three different potencies. Correlation of the pharmacologic response to smoking a marijuana cigarette with plasma THC levels was done with compartmental models and phase plots. It was concluded that the effect compartment for psychologic high is directly coupled to the central (plasma) compartment. It was observed that effect is directly proportional to mean THC levels from approximately 1 to 4 hr after the start of smoking a marijuana cigarette.

Male volunteer subjects smoked one marijuana cigarette containing 100, 200, or 250 micrograms/kg delta-9-tetrahydrocannabinol (THC) and were tested on three perceptual-motor performance measures related to driving. Performance was measured and blood samples were collected for 24 h after smoking. The covariation between pharmacodynamics of performance and pharmacokinetics of THC in plasma was investigated for decrement in performance as the response to smoking a single marijuana cigarette. A significant linear correlation was found between tracking errors under divided attention and THC plasma levels over 5-25 ng/ml for approximately 2 h after smoking. A sigmoid relation was found between critical tracking breakpoint and log THC plasma levels over 2-25 ng/ml for approximately 7 h after smoking.

A biodegradable sustained-release naltrexone bead preparation containing 70% naltrexone in a physical mixture with a copolymer of 90% lactic acid and 10% glycolic acid was evaluated in three male subjects. Each subject received a 10-mg iv dose of naltrexone HCl and a 63-mg dose by subcutaneous implantation of naltrexone beads. Kinetics of naltrexone estimated from the intravenous dose indicated a plasma clearance range of 3.1 to 3.4 l/min and a t 1/2 range of 1.7 to 3.7 hr. After bead implantation, average plasma naltrexone levels were maintained at 0.3 to 0.4 ng/ml and naltrexol levels were at 0.4 to 1.0 ng/ml for a period of approximately 1 mo, during which urine naltrexone and naltrexol levels were about 20 to 30 and 70 to 200 ng/ml. It was estimated that approximately 70% to 77% of the dose was absorbed after bead implantation. There were no serious adverse effects other than tissue irritation in two of the three subjects.

Six subjects each smoked a 1% marijuana cigarette and 2 hr later smoked a second one. Plasma levels of delta-9-tetrahydrocannabinol were measured for 9 hr with a radioimmunoassay. Heart rate and self-reported "high" were measured for 2 hr after each cigarette. All three measures showed a rapid increase after the start of smoking with Cmax occurring before the end of smoking. There was a strong correlation between decrease in heart rate and plasma levels from 10 min after smoking until 120 min. All pharmacodynamic response measures returned to baseline values within approximately 2 hr.

No abstract

No abstract

Quinolone is reported to interact with caffeine, often resulting in an increase both in the plasma half-life and AUC, a decrease in total plasma clearance, and little change in the absorption rate constant and maximum plasma level. These complex changes in the pharmacokinetics of caffeine were analyzed experimentally and from published reports in order to determine the nature of the interaction, which is thought to be due to inhibition of caffeine metabolism by quinolones. A simple pharmacokinetic model for the caffeine-quinolone interaction was developed, which provides a unified method for evaluation and comparison of the effect of quinolones on the disposition of caffeine. The model is applicable to other methylxanthines, such as theophylline. The relative potency of the interactions of quinolones with caffeine in humans has been established as enoxacin (100), pipemidic acid (29), ciprofloxacin (11), norfloxacin (9) and ofloxacin (0).