p -HYDROXYMETHAMPHETAMINE ENANTIOMER PHARMACOKINETICS AND METABOLISM IN RATS: ABSENCE OF N-DEMETHYLATION

✍ Scribed by A. HUTCHALEELAHA; M. MAYERSOHN

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 151 KB
• Volume: 18
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199707)18:5<423::aid-bdd30>3.0.co;2-y

✦ Synopsis

p-hydroxymethamphetamine (OHMAP) is one of the major metabolites of the widely abused drug methamphetamine (MAP). The demethylation of OHMAP to phydroxyamphetamine (OHAP) has been shown in vitro but has never been reported in vivo. The disposition kinetics as well as the metabolism of OHMAP was investigated employing a sensitive HPLC method which can separate the enantiomers of OHMAP and OHAP. Both conjugated and unconjugated forms of these compounds can be quantitated. Male Sprague±Dawley rats were given an iv bolus of racemic OHMAP (20 mg kg 71 ) and serum and urine samples were collected at selected times. The serum concentration±time data for OHMAP enantiomers could be described by a biexponential equation. The clearance of D-OHMAP (93.5 mL min 71 kg 71 ) was slightly, but statistically signi®cantly, greater than that of the L-enantiomer (83´9 mL min 71 kg 71 ). The steady-state volumes of distribution of L-and D-OHMAP were (meanSD) 3´150´84 and 4´231´76 L kg 71 , respectively. No signi®cant concentrations or amounts of OHAP enantiomers could be detected in any serum or urine sample. Rats excreted more unchanged L-OHMAP (34%) than D-OHMAP (29%). In contrast, more conjugated D-OHMAP (57%) was recovered compared to the conjugated L-OHMAP (52%). The results suggest that there is slight stereoselectivity in the disposition of OHMAP enantiomers. The N-demethylation product (OHAP) was not produced in vivo. &1997 by John Wiley & Sons, Ltd.