| Autor: |
Maeda, Yorinobu, Funakoshi, Sachiyo, Nakamura, Mamoru, Fukuzawa, Masataka, Kugaya, Yukimasa, Yamasaki, Miho, Tsukiai, Satsuki, Murakami, Teruo, Takano, Mikihisa |
| Zdroj: |
Clinical Pharmacology & Therapeutics; May 2002, Vol. 71 Issue: 5 p389-397, 9p |
| Abstrakt: |
Our objective was to elicidate the mechanism of pharmacokinetic interaction between lidocaine and mexiletine, because an unexpected increase in plasma lidocaine concentration accompanied by severe side effects was observed when mexiletine was administered to a patient with dilated cardiomyopathy. Plasma concentrations of lidocaine, its major metabolites, and mexiletine were measured in a patient with dilated cardiomyopathy. The lidocaine‐mexiletine interaction was evaluated by examination of the effects ofmexiletine on plasma concentration and the tissue distribution of lidocaine in rabbits in vivo, as well as on the in vitro lidocaine binding to phosphatidylserine, a binding constituent for weakly basic drugs. Plasma lidocaine concentrations increased significantly when the oral dose of mexiletine was increased. This pharmacokinetic interaction was not attributable to a metabolic interaction as evaluated by plasma lidocaine metabolites concentrations. In rabbits, mexiletine seemed to decrease the total plasma clearance of lidocaine, resulting in increased plasma lidocaine concentrations. Mexiletine significantly reduced the tissue distribution of lidocaine to the kidneys and lungs. A strong displacing effect of mexiletine on the binding of lidocaine to phosphatidylserine was observed in vitro. A drug interaction derived from the displacement of lidocaine from tissue binding sites by mexiletine that resulted in the increased plasma lidocaine concentrations was shown. This observation had implicationsfor loading doses and acute effects of lidocaine in the concurrent therapy of lidocaine and mexiletine. Clinical Pharmacology & Therapeutics(2002) 71, 389–397; doi: 10.1067/mcp.2002.124077 |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
Plný text