CLEARANCE OF PHENYTOIN AND VALPROIC ACID IS AFFECTED BY A SMALL BODY-WEIGHT REDUCTION IN AN EPILEPTIC OBESE PATIENT - A CASE-STUDY

The interaction between clearance of phenytoin, valproic acid, phenoba rbital and carbamazepine, and changes in body weight was determined in a 19-year-old obese woman with epilepsy (body weight 93 kg, BMI 36.3 kg/m(2)). The patient, who was given daily oral doses of 100 mg phenob arbital, 350 mg phenytoin, 800 mg valproic acid and 800 mg carbamazepi ne over 5 months was hospitalized for obesity treatment. The daily dos age of each drug was held constant during treatment of the obesity. Bl ood samples were taken five times. Weight reduction was 7 kg (7.5%) ov er 46 days. Estimation of the pharmacokinetic parameters in each drug was performed by Higuchi's Bayesian program, PEDA Pearson's correlatio n coefficient (r) between clearance and body weight Was calculated for each drug. High positive correlations were found between clearance an d body weight for phenytoin (r = 0.800) and valproic acid (r = 0.785), but not for phenobarbital (r = - 0.227) and carbamazepine (r = 0.152) . Clearance of phenytoin and valproic acid may be potentially affected by small changes in body weight.