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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Smoking slows the metabolism of nicotine and accelerates the metabolism of chlorzoxazone. • Nicotine is a useful probe for phenotyping cytochrome P450 2A6 activity and chlorzoxazone is a frequently used probe for CYP2E1 activity. • The tobacco smoke constituents responsible for the reduced CYP2A6 and increased CYP2E1 activities are unknown. WHAT THIS PAPER ADDS • This study demonstrates that CYP2A6 and CYP2E1 activities are not affected by nicotine dosing. • High-dose nicotine treatment has a low potential of interaction with CYP2A6 and CYP2E1 substrates. • The mechanisms of tobacco smoke-elicited changes in CYP2A6 and CYP2E1 activities are yet to be determined. AIMS Smoking slows the metabolism of nicotine and accelerates the metabolism of chlorzoxazone, which are probe reactions for cytochrome P450 2A6 (CYP2A6) and CYP2E1 activities, respectively. We aimed to determine the role of nicotine in these metabolic effects of cigarette smoking. METHODS The study had a single-blind, randomized, crossover two-arm design. Twelve healthy smokers were given two transdermal patches with 42-mg nicotine a day or placebo patches, each for 10 days. The subjects abstained from smoking during the study arms. Oral chlorzoxazone was given on day 7 and deuterium-labelled nicotine-d2 and cotinine-d4 infusion on day 8. RESULTS There was no significant influence of transdermal nicotine administration on pharmacokinetic parameters of nicotine-d2 or on the formation of cotinine-d2. Nicotine decreased the volume of distribution (62.6 vs. 67.7 l, 95% confidence interval of the difference −9.7, −0.6, P= 0.047) of infused cotinine-d4. There were no significant differences in disposition kinetics of chlorzoxazone between the treatments. CONCLUSIONS CYP2A6 and CYP2E1 activities are not affected by nicotine. The tobacco smoke constituents responsible for the reduced CYP2A6 and increased CYP2E1 activities remain unknown. [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Methamphetamine (MA) is a chiral compound. • The S-(+) enantiomer is more commonly abused and is more potent in producing central nervous system and cardiovascular effects than the R-(−) enantiomer. • Studies describing the metabolism of MA have mainly been done with the S-(+)-isomer; pharmacokinetic data for R-(−)-MA or racemic MA are very limited. WHAT THIS STUDY ADDS • Stereoselectivity exists in the metabolism of MA. • Urinary excretion of para hydroxymethamphetamine (pOH-MA) was found to be least affected by stereoselectivity. • It is suggested that pOH-MA may be a more stable biomarker of MA abuse. AIM To characterize the formation and urinary elimination of metabolites of S-(+) and R-(−) methamphetamine (MA) in humans. METHODS In this 12-subject, six-session, double-blind, placebo-controlled, balanced, crossover design study, the formation of the MA metabolites para hydroxymethamphetamine (pOH-MA) and amphetamine (AMP) were determined in urine after intravenous doses of S-(+)-MA 0.25 and 0.5 mg kg−1, R-(−)-MA 0.25 and 0.5 mg kg−1, racemic MA 0.5 mg kg−1, or placebo. Parent drug and metabolite levels in urine and plasma were measured by gas chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental models using WinNonlin. RESULTS An approximately threefold enantioselectivity difference in elimination was observed for AMP, with 7% of the dose converted to S-(+)-AMP vs. 2% to R-(−)-AMP ( P < 0.001). Furthermore, less R-(−)-pOH-MA was excreted in the urine compared with S-(+)-pOH-MA (8% vs. 11%, P= 0.02). Correspondingly, S-(+)-MA excretion was less than R-(−)-MA (42% vs. 52%; P= 0.005). CONCLUSIONS The metabolism of MA is enantioselective, with formation of AMP having the highest isomer selectivity. A greater percentage of MA is converted to pOH-MA (8–11%) than AMP (2–7%). The formation of pOH-MA was less affected by the MA enantiomer administered, suggesting that urine pOH-MA may be a more stable biomarker of MA metabolism. [ABSTRACT FROM AUTHOR]

1. The purpose of the present study was to determine whether the consumption of an acute dose of caffeine andMa Huangincreases resting energy expenditure (REE), heart rate (HR) and blood pressure (BP) over a 3 h period.2. A randomized, double-blind cross-over study was performed evaluating the acute effects of caffeine (150 mg)/herbal ephedra (Ma Huang; 20 mg ephedra alkaloids) versus a placebo. A total of eight healthy subjects (four males and four females) with a mean (±SD) age of 23.4 ± 0.8 years (mean ages for males and females: 25.3 ± 0.7 and 22.0 ± 0.7 years, respectively) and 22.5 ± 3.1% body fat (15.7 ± 1.2 and 27.6 ± 3.5% body fat for males and females, respectively) were recruited to the study. Participants were moderate caffeine users (approximately 150–300 mg/day).3. Subjects reported to the laboratory following a 12 h fast and 48 h of a caffeine-free diet. Resting energy expenditure was measured prior to supplementation and for 15 min every 30 min for 3 h following supplementation. Heart rate and BP were obtained every 15 min. Blood samples were obtained every 30 min following the measurement of REE and analysed for caffeine, ephedrine, free fatty acids and glucose.4. By 3 h, HR was 22.7 ± 5.5% higher (P < 0.05) than baseline for the caffeine/ephedra trial compared with 8.9 ± 2.2% higher for the placebo grou. At 3 h, systolic BP was 9.1 ± 2.2% higher (P < 0.05) than baseline for the caffeine/ephedra trial compared with only 1.9 ± 2.9% different from baseline for the placebo trial. There was no effect of the caffeine/ephedra combination on diastolic BP. Resting energy expenditure during the last 30 min was 4.5 ± 2.5% higher in the placebo trial and 10.7 ± 2.5% higher (P < 0.05) in the caffeine/ephedra trial; REE was 8.5 ± 2.0% higher (P < 0.05) in the caffeine/ephedra trial compared with the placebo trial. Free fatty acids increased over time in the placebo and caffeine/ephedra trials (from 0.5 ± 0.05 to 0.63 ± 0.05 mEq/L and from 0.48 ± 0.06L to 0.8 ± 0.05 mEq/L, respectively).5. Caffeine and herbal ephedra, at doses of 150 mg and 20 mg (ephedrine), respectively, result in a significant elevation in REE, HR and BP. Although significant, the increase in energy expenditure is negligible in terms of weight loss. [ABSTRACT FROM AUTHOR]

Presents the study on saliva cotinine using different methods to estimate nicotine intake and the implication of the laboratories' use of different methods of collection. Methods used in the study; Results of the study; Conclusions.

The article discusses a study on the disposition kinetics of nicotine and cotinine at doses that are consistent with intake of nicotine during secondhand smoke (SHS) exposure. The study, which was participated by sixteen healthy non-smokers, took place at the clinical research centre at San Francisco General Hospital, wherein subjects are given intervenous infusions of deuterium labelled nicotine and cotinine. It reveals no evidence of dose-related differences in nicotine and cotinine kinetics

A letter to the editor is presented which discusses a study regarding the effect of nicotine on the activity of cytochrome P450 1A2 (CYP1A2).

Presents a letter to the editor about the effect of pregnancy on a measure of FMO3 activity.

Aim: To characterize the formation and urinary elimination of metabolites of S-(+) and R-(-) methamphetamine (MA) in humans., Methods: In this 12-subject, six-session, double-blind, placebo-controlled, balanced, crossover design study, the formation of the MA metabolites para hydroxymethamphetamine (pOH-MA) and amphetamine (AMP) were determined in urine after intravenous doses of S-(+)-MA 0.25 and 0.5 mg kg(-1), R-(-)-MA 0.25 and 0.5 mg kg(-1), racemic MA 0.5 mg kg(-1), or placebo. Parent drug and metabolite levels in urine and plasma were measured by gas chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental models using WinNonlin., Results: An approximately threefold enantioselectivity difference in elimination was observed for AMP, with 7% of the dose converted to S-(+)-AMP vs. 2% to R-(-)-AMP (P < 0.001). Furthermore, less R-(-)-pOH-MA was excreted in the urine compared with S-(+)-pOH-MA (8% vs. 11%, P= 0.02). Correspondingly, S-(+)-MA excretion was less than R-(-)-MA (42% vs. 52%; P= 0.005)., Conclusions: The metabolism of MA is enantioselective, with formation of AMP having the highest isomer selectivity. A greater percentage of MA is converted to pOH-MA (8-11%) than AMP (2-7%). The formation of pOH-MA was less affected by the MA enantiomer administered, suggesting that urine pOH-MA may be a more stable biomarker of MA metabolism.