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2748664 
Technical Report 
Species differences in phenazepam kinetics and metabolism 
Zherdev, VP; Caccia, S; Garattini, S; Ekonomov, AL 
1982 
IPA/86/653232 
J 
REF 15 
191-196 
English 
IPA COPYRIGHT: ASHP The pharmacokinetic profiles of oral phenazepam (I) and 3-hydroxyphenazepam (II) were compared in rat, dog, cat and man following administration of single oral doses of I; 3 or 5 mg doses were given to 3 healthy volunteers. The absorption of I was reasonably rapid in all the species studied. Blood peak concentrations were reached at 0.5-2 h in the animals but only at 4 h in man, 0.038 mcg/ml at the highest doses tested. The largest normalized (value/dose) Cmax and AUC were observed in man, while the rat gave the lowest values. The half-life of I was about 60 h in man and 6.35 +- 2.32 to 13.72 +- 2.09 h in the animals. 3-Hydroxyphenazepam was rapidly detected in the animals but no measureable amounts (|LT/3 ng/ml) were found in human blood. At the oral doses tested, the ratio of the AUC for II to I was 0.01, 0.48, and 0.53 in the dog, rat, and cat, respectively. The half-life of the metabolite was shorter than that of I in the dog, it was comparable in the rat and longer in the cat. The metabolite might contribute to the overall pharmacological effects of I in those species in which it accumulates in significant amounts.