Effects of Ketamine Anesthesia on Phenytoin Biodisposition

Abstract

After oral administration (10% suspension in arabic gum, at 500 mg/kg), total phenytoin (PHT) concentrations were measured in the blood and brain of rats anesthetized with ketamine (60 mg/kg, intraperitoneally i.p.) and in a control group that received only PHT. The concentration of PHT in blood and brain was significantly higher in the ketamine than in the control group. At 1, 1.5, 2, and 3 h, increased brain PHT reflected increased blood concentrations. At all times, the plasma protein binding of PHT was similar in both groups. After intravenous (i.v.) administration, instead, at 10 mg/kg, total PHT concentrations were similar in rats anesthetized with ketamine (60 mg/kg, i.p.) and in a control group that received only PHT under mild ether anesthesia. Thus, the main factor involved with the altered PHT biodisposition caused by ketamine anesthesia appears to be increased absorption of the drug.

Biliary clearance of bromosulfophthalein in anesthetized and freely moving conscious rat

“…Several reports for pharmacokinetic interaction with ketamine have been published for propofol [16], chylomicron [17,18], cocaine [19], verapamil [20] and phenytoin [21], and these results have a connection with the induced cytochrome P450 (CYP) by ketamine [16,22]. Similarly, Zoletil was also proved to increase CYP2B and CYP3A isoforms [23].…”