Steady-state pharmacokinetics and electrocardiographic pharmacodynamics of clarithromycin and loratadine after individual or concomitant administration
| Autor: | J. Carl Craft, Harry Shi, Gustavson Linda E, Stuart I. Harris, Robert A. Carr, Anthony Edmonds, Charles Locke, Palmer Robert N |
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| Rok vydání: | 1998 |
| Předmět: |
Adult
Male Adolescent Pharmacology Loratadine Electrocardiography Pharmacokinetics Double-Blind Method Oral administration Clarithromycin Anti-Allergic Agents medicine Humans Pharmacology (medical) Drug Interactions Active metabolite Antibacterial agent Analysis of Variance Cross-Over Studies Chemistry Crossover study Anti-Bacterial Agents Drug Combinations Infectious Diseases Pharmacodynamics medicine.drug |
| Zdroj: | Antimicrobial agents and chemotherapy. 42(5) |
| ISSN: | 0066-4804 |
| Popis: | To evaluate the potential for an interaction between clarithromycin and loratadine, healthy male volunteers ( n = 24) received each of the following regimens according to a randomized crossover design: 500 mg of clarithromycin orally every 12 h (q12h) for 10 days, 10 mg of loratadine orally q24h for 10 days, and the combination of clarithromycin and loratadine. A washout interval of 14 days separated regimens. The addition of loratadine did not statistically significantly affect the steady-state pharmacokinetics of clarithromycin or its active metabolite, 14( R )-hydroxy-clarithromycin. However, the addition of clarithromycin statistically significantly altered the steady-state maximum observed plasma concentration and the area under the plasma concentration-time curve over a dosing interval for loratadine (+36 and +76%, respectively) and for descarboethoxyloratadine (DCL), the active metabolite of loratadine (+69 and +49%, respectively). Clarithromycin probably inhibits the oxidative metabolism of loratadine and DCL by the cytochrome P-450 3A subfamily. Electrocardiograms ( n = 12) were obtained over 24-h periods at baseline and steady state (day 10). The mean maximum QTc interval and area under the QTc interval-time curve on day 10 were modestly increased ( |
| Databáze: | OpenAIRE |
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