In vitro characterization of the inhibition profile of loratadine, desloratadine, and 3-OH-desloratadine for five human cytochrome P-450 enzymes
| Autor: | M E, Barecki, C N, Casciano, W W, Johnson, R P, Clement |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Cytochrome P-450 CYP1A2 Inhibitors
In Vitro Techniques Loratadine Mixed Function Oxygenases Cytochrome P-450 CYP2C19 Steroid 16-alpha-Hydroxylase Cytochrome P-450 CYP1A2 Cytochrome P-450 CYP2D6 Inhibitors Steroid Hydroxylases Histamine H1 Antagonists Cytochrome P-450 CYP3A Cytochrome P-450 Enzyme Inhibitors Humans Aryl Hydrocarbon Hydroxylases Enzyme Inhibitors Cytochrome P-450 CYP2C9 |
| Zdroj: | Drug metabolism and disposition: the biological fate of chemicals. 29(9) |
| ISSN: | 0090-9556 |
| Popis: | 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 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 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. |
| Databáze: | OpenAIRE |
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