Intravenous phenytoin loading in patients after neurosurgery and in status epilepticus. A population pharmacokinetic study.
In 49 patients treated with intravenous phenytoin after a neurosurgical procedure or because of repetitive frequent seizures, the serum concentration was measured before and 2 hours after an intravenous bolus injection. Based on these data the apparent volume of distribution and intra- and interpatient variability were determined in this representative patient population, using the statistical package NONMEM. From 5 characteristics tested (age, sex, bodyweight, serum albumin, renal function) only bodyweight was found to significantly influence the apparent volume of distribution of phenytoin. The population average was estimated as 1.0 +/- 0.04 L/kg (estimate +/- SE) and interindividual variability, expressed as coefficient of variation, was 23 +/- 6%. By means of Monte Carlo simulations an optimal dosing scheme for phenytoin loading has been calculated. Based on these results, a dose of 15 mg/kg divided into 3 intravenous injections administered 2 hours apart at a maximum rate of 50 mg/min is recommended. This loading regimen should result in therapeutic concentrations (10 to 20 mg/L) in 90% of patients within 6 hours.
Vozeh
S
S
Department of Internal Medicine, University Hospital (Kantonsspital), Basel.
Uematsu
T
T
Aarons
L
L
Maitre
P
P
Landolt
H
H
Gratzl
O
O
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009493:Neurosurgery; D010672:Phenytoin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D013226:Status Epilepticus / Q000188:drug therapy*
D010672:Phenytoin