Phenytoin Pharmacokinetics After Intravenous Administration to Patients Receiving Enteral Tube-Feeding

Serial plasma samples were collected after administration of 13 intravenous dose 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 loner than 5 days (group 2). Average plasma phenytoin concentrations were higher in group 1 than in group 2 (0.003). The median intravenous study dose was the same (300 mg) in both groups (p=0.17). 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 patients receiving long-term enteral feeding. V-max was higher in group 2 than in group 1 (medians, 709 versus 394 mg/day) and K-m smaller (medians, 2.5 versus 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 long-term enteral feeding it would be advisable to decrease the dosing interval as well as increasing the phenytoin dose when the drug is administered intravenously