Ms. Alhumayyd, PHARMACOKINETIC INTERACTIONS BETWEEN ERYTHROMYCIN, CLARITHROMYCIN, ROXITHROMYCIN AND PHENYTOIN IN THE RAT, Chemotherapy, 43(2), 1997, pp. 77-85
The effects of the macrolide antibiotics, erythromycin, clarithromycin
and roxithromycin, on the pharmacokinetic profile of phenytoin were s
tudied 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 r
oxithromycin (100 mg/kg) were given by the oral route. The concentrati
ons of phenytoin in plasma were determined using a high-performance li
quid chromatographic method. The area under the curve the maximum plas
ma concentration and the elimination half-life (t(1/2)) of phenytoin w
ere 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-drag interaction may occur if phenytoin is administered
concurrently with erythromycin, clarithromycin or roxithromycin.