摘要：

The purpose of this study was to evaluate loratadine, desloratadine, and 3-OH-desloratadine as inhibitors of certain liver enzymes. Pooled liver were used to determine whether loratadine, desloratadine, and 3-OH-desloratadine were inhibitors of () 1A2, 2C9, 2C19, 2D6, and 3A4. Loratadine did not inhibit or at concentrations up to 3829 ng/ml, which is approximately 815-fold greater than the expected maximal plasma concentration (4.7 +/- 2.7 ng/ml) following the recommended dose of 10 mg/day. Loratadine inhibited and with IC(50) values of approximately 0.76 microM [291 ng/ml; K(i) congruent with 0.61 microM (234 ng/ml)] and 8.1 microM [3100 ng/ml; K(i) congruent with 2.7 microM (1034 ng/ml)], respectively, which are approximately 62 and 660 times the expected loratadine therapeutic exposure concentration. Neither desloratadine nor 3-OH-desloratadine inhibited , , , , or greater than 25% at concentrations of 3108 or 3278 ng/ml, respectively. These results suggest that loratadine and the active metabolites desloratadine and 3-OH-desloratadine are unlikely to affect the pharmacokinetics of coadministered drugs which are metabolized by these five enzymes.

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