CIPROFLOXACIN DECREASES PLASMA PHENYTOIN CONCENTRATIONS IN THE RAT

The pharmacokinetic interaction between phenytoin and ciprofloxacin wa s studied in rats. One group of animals was given phenytoin (20 mg/kg, p.o.) as a single daily dose for 7 days. In another group of animals, the same protocol was followed except that ciprofloxacin was given in two equal doses (15 mg/kg, i.p., each) on days 5, 6 and 7. On day 8, phenytoin blood sampling was performed at 0.083, 0.25, 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 10.0 and 12.0 h. Similarly, urine samples were collecte d at 4, 6 and 8 h following drug administration from the same animals that had received either phenytoin alone or phenytoin together with ci profloxacin. The concentrations of phenytoin in the plasma and urine w ere measured using an HPLC method. Ciprofloxacin significantly (P < 0. 05) reduced the area under the curve (AUG), the maximum plasma concent ration (C-max)and the elimination half-life (t(1/2)) of phenytoin. Add itionally, ciprofloxacin increased phenytoin concentrations in urine a t 4, 6 and 8 h. These results show that ciprofloxacin decreases the pl asma levels of phenytoin when the two drugs are given concurrently.