Stereoselective pharmacokinetics of methadone in beagle dogs.
The pharmacokinetics of methadone were studied in beagle dogs (n = 4) following intravenous administration of the racemate (0.5 mg/kg) and of the individual (R)-(0.25 mg/kg) and (S)-enantiomers (0.25 mg/kg) using a stereospecific HPLC assay. There was no significant difference between the pharmacokinetic parameters of (R)-methadone and (S)-methadone following administration of the individual enantiomers. Stereoselective differences were evident following administration of the racemate (P values for differences in AUC and CL were 0.01 and 0.046, respectively) and the clearance of the (S)-enantiomer was increased when administered as part of the racemate (316 +/- 81 vs 487 +/- 128 ml/min, P = 0.04). The data suggest that stereoselective disposition including potential enantiomer-enantiomer interactions should be considered in pharmacokinetic-pharmacodynamic studies of (R,S)-methadone.
Schmidt
N
N
Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany.
Brune
K
K
Williams
K M
KM
Geisslinger
G
G
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D007275:Injections, Intravenous; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D013237:Stereoisomerism
D008691:Methadone