Examples of intersubject variability in induction
Experimental System | Inducer and Treatment | Endpoints Measured | Reference |
|---|---|---|---|
| Healthy volunteers | for 22 days, racemic mephenytoin at 0 and 22 days | Increase in urinary mephenytoin R/S ratio; from no increase to 8-fold increase | Zhou et al (1990) |
| Healthy volunteers | Rifampin for 5 days, triazolam at 0 and 6 days | After induction, the plasma triazolam AUC in subjects decreased to 1% to 12%, a 12-fold variation | Villikka et al (1997) |
| Patients with normal hepatic and renal function | Rifampin for 4 days, 14C-erythromycin at 0 and 4 days | Increase in 14CO2 by breath test; from 20% to 400% increase | Watkins et al (1989) |
| Biopsy of small bowel mucosa from healthy volunteers | Rifampin for 7 days | CYP3A4 mRNA, from no increase to 11-fold increase | Kolars et al (1992) |
| Liver microsomes from patients with digestive tumors | Omeprazole for 4 days, microsomes prepared from liver biopsy samples before and after treatment | Microsomal CYP1A2 content increased by 2- to 8-fold, 1A2-related enzyme activities increased by 2- to 7-fold | Diaz et al (1990) |