Use of Three Probes to Assess the Influence of Sex on Hepatic Drug Metabolism

Abstract

Clearances of phenytoin (PHT), ethosuximide, and theophylline were estimated by a single-dose, single-sample strategy in healthy, young adult men and women. PHT concentrations were measured in salivary ultrafiltrates, ethosuximide concentrations were measured in saliva, and theophylline concentrations were measured in plasma. Estimates of the clearances of these three probes of hepatic drug-metabolizing enzymes revealed a trend toward slightly lower clearances among women compared to men: mean PHT clearance 15 % lower, ethosuximide clearance 27% lower, and theophylline clearance 14% lower. However, only differences in ethosuximide clearances were statistically significant. The use of oral contraceptive steroid (OCS) drugs on PHT and ethosuximide clearance was examined, and no significant effects were detected.

Has bovine somatotropin (BST) an effect upon drug disposition? Comparative studies in goats and cattle with sulphadimidine and antipyrine after parenteral administration of BST, zeranol and proligestone

“…This interaction can be the result of an altered fate of the drugs in the organism, or the consequence of pharmacodynamic synergism or antagonism. In women, oral contraceptives have been shown to signifi-cantly change the clearance of several drugs (Briggs & Briggs, 1981;Abernathy et al, 1982;Legner & Bennet, 1982;Jochemsen et al, 1982;Teunissen et al, 1982;Tornatore et al, 1982;Stoehr et al, 1984; Van der Kuy & Merkus, 1987;Bachmann et al, 1987) and this therefore confirms the general finding in laboratory species that low doses of sex hormones can affect drug disposition. In the rat, the duration and intensity of drug action is often greater in the adult female than in the adult male (Conney, 1974;Kato, 1974;Gustafsson el al., 1983;Kane & Chen, 1987;Trenk et al, 1988;Waxman, 1988).…”

“…The existence of sex differences in drug disposition has been demonstrated in other species as well (Krasavage & Michaelson, 1965;Vogin et al, 1966;Scotti, 1973;Van den Berg et al, 1978;Brown & Greene, 1980;Erichsen et al, 1980;Stegeman & Chevion, 1980;Teunissen et al, 1982;Greenblatt et al, 1985;Miners et al, 1986;Bachmann et al, 1987) but the differences do not seem to be as marked as in the rat. Furthermore, the sexual dimorphism in the metabolism of xenobiotics observed in the rat is not representative of other species (Gustafsson et al, 1983;Niedermeyer & Shapiro, 1988).…”