Rajneesh P. Nath

Buprenorphine Pharmacokinetics: Relative Bioavailability of Sublingual Tablet and Liquid Formulations

Buprenorphine is an effective new treatment for opiate dependence. This study compared the bioavailability of buprenorphine from a tablet to that from a reference solution. Six men experienced with, but not dependent on, opiates (DSM‐III‐R) were each administered 7.7 mg of buprenorphine in liquid form and 8 mg in tablet form 1 week apart in a balanced crossover design. Plasma levels were measured by electron capture capillary gas chromatography (GC), and concentration‐time curves were constructed. Pharmacokinetic data were analyzed by analysis of variance. The bioavailability from the tablet was approximately 50% that from the liquid and was not affected by saliva pH. Lower bioavailability from the tablet may be due to slow dissolution.

Buprenorphine and naloxone combinations: the effects of three dose ratios in morphine-stabilized, opiate-dependent volunteers.

Abstract Sublingual buprenorphine is a promising new treatment for opiate dependence, but its opioid agonist effects pose a risk for parenteral abuse. A formulation combining buprenorphine with the opiate antagonist naloxone could discourage such abuse. The effects of three intravenous (IV) buprenorphine and naloxone combinations on agonist effects and withdrawal signs and symptoms were examined in 12 opiate-dependent subjects. Following stabilization on a daily dose of 60 mg morphine intramuscularly, subjects were challenged with IV doses of buprenorphine alone (2 mg) or in combination with naloxone in ratios of 2:1, 4:1, and 8:1 (1, 0.5, or 0.25 mg naloxone), morphine alone (15 mg) or placebo. Buprenorphine alone did not precipitate withdrawal and had agonist effects similar to morphine. A naloxone dose-dependent increase in opiate withdrawal signs and symptoms and a decrease in opioid agonist effects occurred after all drug combinations. Buprenorphine with naloxone in ratios of 2:1 and 4:1 produced moderate to high increases in global opiate withdrawal, bad drug effect, and sickness. These dose ratios also decreased the pleasurable effects and estimated street value of buprenorphine, thereby suggesting a low abuse liability. The dose ratio of 8:1 produced only mild withdrawal symptoms. Dose combinations at 2:1 and 4:1 ratios may be useful in treating opiate dependence.

Human pharmacology of the methamphetamine stereoisomers.

To help predict the consequences of precursor regulation, we compared the pharmacokinetics and pharmacodynamics of the methamphetamine (INN, metamfetamine) stereoisomers.

Delayed disposition of cocaine in sweat patches and in skin blister: cocaine may migrate from plasma to sweat patches via interstitial fluid

Sweat patch analysis is extensively used for drug abuse monitoring. The present study investigates how cocaine migrates to sweat patches. In the cumulative collection model, the drug absorption rate in patches should be proportional to the drug concentration in the preceding disposition compartment if drug back‐transfer is negligible. Therefore, we measured the slopes of cocaine concentration curves in patches as a marker for absorption rate (into patches) after a single dose of cocaine‐d5 (1mg/kg over 60 min) in healthy cocaine users (n=5). Patches were placed on the back of subjects prior to drug administration and removed at 0–72 hr postdose. Blood and interstitial fluid (skin blister fluid) were collected up to 72 hr. Patch cocaine levels showed semi‐cumulative collection with peaks between 8 and 48 hr. Cocaine levels in plasma and interstitial fluid peaked at 1.0±0 and 5.3±0.6 hours postdose, respectively, suggesting a delayed cocaine disposition in the interstitial fluid. Similarly, patch cocaine absorption was delayed with rate peaks at 4.3±2.9 hr postdose. Tmax for plasma benzoylecgonine (BE) was 5.0±2.4 hr. BE also showed a delayed peak in the interstitial fluid at 11.3±11.0 hr post, and the highest BE absorption in patches was observed in a similar time range of 12.4±4.9 hr. Cocaine and its metabolite migrate into patches in a time period that coincides with Tmax in interstitial fluid. Cocaine seems to travel from plasma to sweat patches via interstitial fluid.

Pharmacokinetics of intravenous d- and l-methamphetamine in healthy volunteers

Methamphetamine has a chiral structure. The aim of the present study was to assess the pharmacokinetics of methamphetamine enantiomers in humans.

Three Day 12-Hour Cocaine Infusion Produces Tolerance in Cardiovascular and Subjective Effects, But Does Not Alter Cocaine Self-Administration Behavior in Humans

Clinical Pharmacology & Therapeutics (2003) 73, P91–P91; doi:

Suboxone: A Comparison of Dosing Regimens and in Vivo Dissolution Times With Two Different Sublingual Tablet Formulations

Clinical Pharmacology & Therapeutics (2003) 73, P36–P36; doi:

The Cardiovascular Effects of D- and L-Methamphetamine

Clinical Pharmacology & Therapeutics (2003) 73, P36–P36; doi:

Sustained 3-Day Intravenous Cocaine Exposure Decreases Appetite and Hunger But Does Not Alter Food Intake Patterns in Cocaine-Dependent Volunteers

Clinical Pharmacology & Therapeutics (2003) 73, P35–P35; doi: