Abstract
1. Single sample clearance estimates, Čl, were calculated for each of five drugs employed as probes of hepatic drug-metabolizing activity in rats. Probe drugs were theophylline, phenytoin, valproic acid, antipyrine, and S-warfarin. Čl values were calculated for each probe in animals pretreated with phenobarbital, isosafrole, β-naphthoflavone, or clofibrate. Control animals were pretreated with vehicle only.
2. A clearance index (c.i., probe Čl after pretreatment divided by probe Čl control) was calculated for each probe and each pretreatment regimen, and data were consolidated to give different probe-based handprints of the pretreatment effects.
3. S-Wartarin was the least specific probe as its c.i. was greater than 1˙0 subsequent to each pretreatment. Theophylline appeared to be the most selective probe since its c.i. deviated significantly from unity (3˙56) only after β-naphthoflavone pretreatment. Phenytoin exhibited c.i. values less than unity after each pretreatment indicating that it may not, when used as a single sample probe of hepatic drug-metabolizing activity, effectively discriminate between inductive or inhibitory effects of xenobiotics.
4. Multi-probe-based handprints of hepatic drug-metabolizing activity structured from simple single sample estimates of probe clearance have potential in the rapid screening of xenobiotic-induced alterations of drug-metabolizing enzyme activity.