title: Pharmacokinetic interactions between erythromycin, clarithromycin, roxithromycin and phenytoin in the rat.
abstract: The effects of the macrolide antibiotics, erythromycin, clarithromycin and roxithromycin, on the pharmacokinetic profile of phenytoin were studied in rats. Animals were injected with phenytoin (100 mg/kg, i.p.) daily for 4 days and then they were given phenytoin (20 mg/kg, i.p.) alone or the same dose of phenytoin together with erythromycin (50 mg/kg, i.p.), clarithromycin (50 mg/kg, i.p.) or roxithromycin (50 mg/kg, i.p.). In another set of experiments, the same protocol was followed except that erythromycin (100 mg/kg), clarithromycin (100 mg/kg) and roxithromycin (100 mg/kg) were given by the oral route. The concentrations of phenytoin in plasma were determined using a high-performance liquid chromatographic method. The area under the curve the maximum plasma concentration and the elimination half-life (t1/2) of phenytoin were significantly (p < 0.05) increased by the macrolides. In addition, the macrolides significantly (p < 0.05) reduced the level of hepatic cytochrome P-450 in the rats. These results suggest that a potentially harmful drug-drug interaction may occur if phenytoin is administered concurrently with erythromycin, clarithromycin or roxithromycin.
authors.affiliation: Department of Medical Pharmacology, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
authors.forename: M S
authors.initials: MS
authors.lastname: al-Humayyd
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D000927:Anticonvulsants / Q000493:pharmacokinetics; D017291:Clarithromycin / Q000493:pharmacokinetics*; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D004917:Erythromycin / Q000493:pharmacokinetics*; D006400:Hematocrit; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D010672:Phenytoin / Q000097:blood / Q000493:pharmacokinetics*; D019338:Polypharmacy; D051381:Rats; D017208:Rats, Wistar; D015575:Roxithromycin / Q000493:pharmacokinetics*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D000927:Anticonvulsants; D015575:Roxithromycin; D010672:Phenytoin; D004917:Erythromycin; D003577:Cytochrome P-450 Enzyme System; D017291:Clarithromycin