Vol. 29, Issue 9, 1173-1175, September 2001

SHORT COMMUNICATION
In Vitro Characterization of the Inhibition Profile of Loratadine, Desloratadine, and 3-OH-Desloratadine for Five Human Cytochrome P-450 Enzymes

Mary E. Barecki, Christopher N. Casciano, William W. Johnson, and Robert P. Clement

Department of Drug Metabolism and
Pharmacokinetics,
Schering-Plough Research Institute,
Lafayette, New Jersey

The purpose of this study was to evaluate loratadine, desloratadine, and 3-OH-desloratadine as inhibitors of certain human liver cytochrome P-450 enzymes. Pooled human liver microsomes were used to determine whether loratadine, desloratadine, and 3-OH-desloratadine were inhibitors of cytochrome P-450 (CYP) 1A2, 2C9, 2C19, 2D6, and 3A4. Loratadine did not inhibit CYP1A2 or CYP3A4 at concentrations up to 3829 ng/ml, which is approximately 815-fold greater than the expected maximal human plasma concentration (4.7 ± 2.7 ng/ml) following the recommended dose of 10 mg/day. Loratadine inhibited CYP2C19 and CYP2D6 with IC₅₀ values of approximately 0.76 µM [291 ng/ml; K_i  0.61 µM (234 ng/ml)] and 8.1 µM [3100 ng/ml; K_i  2.7 µM (1034 ng/ml)], respectively, which are approximately 62 and 660 times the expected loratadine therapeutic exposure concentration. Neither desloratadine nor 3-OH-desloratadine inhibited CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 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 cytochrome P-450 enzymes.