Pharmacokinetics of the PDGF-antagonist trapidil in patients with and without renal impairment.

The pharmacokinetics of the PDGF-antagonist trapidil and its major metabolite desethyltrapidil (M 1) were studied in patients with and without renal failure after a single dose of 200 mg and following 4-day treatment with 200 mg t. i. d. Twenty patients were classified according to their renal function as assessed by creatinine clearance (C Cr ) in group A: 133.7 ± 30.3 ml/min (n = 8), group B: 63.6 ± 15.4 ml/min (n = 6) and group C: 17.9 ± 6.1 ml/min (n = 6), patients on hemodialysis were not enrolled. After the first dose maximal plasma concentrations of trapidil with 5.99 ± 1.60 (A), 5.76 ± 1.46 (B) and 5.63 ± 1.53 μg/ml (C) were not different between groups, but somewhat lower on day 4 with 4.96 ± 0.78 (A), 5.78 ± 1.78 (B) and 5.47 ± 1.42 μg/ml (C). Similarly, AUC 0- ∞-values on day I with 16.9 ± 4.8 (A), 20.2 ± 6.7 (B) and 22.2 ± 11.2 μg/ml X h (C) showed only modest (NS) differences between groups, but decreased markedly on day 4 to 10.8 ± 1.8 (A), 13.6 ± 5.8 (B) and 14.4 ± 4.3 μg/ml X h (C). Linear regression analysis between AUC and C Cr demonstrated no relationship between these parameters. For plasma concentrations of M 1 no significant differences were seen between groups. At steady state maximal plasma concentrations of M I occurred earlier and were slightly increased. In one patient (group B) receiving tamoxifen comedication markedly elevated plasma concentrations of trapidil and desethyltrapidil occurred, suggesting a pharmacokinetic interaction. Trapidil may be safely given to patients with impaired renal function, the apparent decrease of trapidil plasma concentrations may suggest autoinduction of metabolizing enzymes.