Clinical evaluation of a predictive model for phenytoin plasma concentrations
- LK Pulver, SE Tett, WS. Montgomery
- Aust J Hosp Pharm 1991;21:303-7
Serial plasma samples were collected after administration of 13 intravenous doses of phenytoin to 11 patients with head injury; 5 to patients who had been receiving enteral feeds for less than 5 days (group 1), and 8 to patients who had been receiving enteral feeds for longer than 5 days (group 2). Average plasma phenytoin concentrations were higher in group 1 than in group 2 (p=0.003). The median intravenous study dose was the same (300 mg) in both groups (p=0.1 7). Group 2 received slightly higher doses expressed as mg/kg (median of 5.45 mg/kg compared to 4.29 mg/kg in group 1, p=0.21). Phenytoin was more rapidly eliminated following intravenous dosing in patients receiving long-term enteral feeding.V max was higher in group 2 than in group 1 (medians, 709versus 394 mg/day) andK m smaller (medians, 2.5versus 3.9 mg/l), but volume of distribution was similar in both groups (p=0.88). The kinetic parameters of phenytoin in group 1 were similar to previously published population pharmacokinetic parameters. In order to maintain phenytoin concentrations adequate for seizure prophylaxis in patients receiving longterm enteral feeding it would be advisable to decrease the dosing interval as well as increasing the phenytoin dose when the drug is administered intravenously.