Pharmacokinetic differences of desmethyldiazepam in three outbred Wistar strains related to differences in liver enzyme activities.
Various strains of rats differ in their sensitivities towards benzodiazepines suggesting that variations in biological features are responsible for these differences. All reports concern inbred strains. We have studied male rats of three outbred Wistar strains with regard to the pharmacokinetics of desmethyldiazepam given as a single intravenous dose. The elimination half-life of desmethyldiazepam was longer in the Riv:TOX(M) (from the National Institute of Public Health and Environmental Protection) and in the Cpb:WU strain than in the Crl:(WI)BR strain. This strain difference in elimination of desmethyldiazepam may be related to differences in liver enzyme activities.
van der Laan
J W
JW
Laboratory for Medicines and Medical Devices, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
de Groot
G
G
Wortelboer
H
H
Noordhoek
J
J
D000818:Animals; D019363:Cytochrome P-450 CYP1A1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D003708:Nordazepam / Q000493:pharmacokinetics*; D010088:Oxidoreductases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D003708:Nordazepam; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D019363:Cytochrome P-450 CYP1A1