Weight gain in epileptic patients during treatment with valproic acid: a retrospective study.

BACKGROUND: Weight gain has been recognized as a common adverse effect of valproic acid (VPA) that leads to discontinuation in some patients but its incidence and correlates have been rarely studied. METHODS: We have analyzed the records retrospectively and interviewed 70 adult patients attending an epilepsy clinic on VPA mono- or polytherapy followed over a median of 27 months (range 3-189), as well as 20 patients on carbamazepine (CBZ) monotherapy. Patients were divided into non-weight gainers (< 5% baseline body weight), mild-moderate weight gainers (5-10% body weight) and marked weight gainers (> 10% body weight). The following variables were statistically analyzed to determine their relationship to weight gain: gender, age, body mass index, drug dose, personal or family history of obesity and monotherapy versus polytherapy. RESULTS: Seventy-one percent of the VPA group were weight gainers versus 43% in the CBZ group. A weight gain of more than 4 kg in 70% of the VPA group was observed. The weight gain was often sustained and frequently socially significant to the patients. Patients below or within normal range body mass index prior to the start of VPA experienced the most severe percentage weight gain. From the structured patient interviews, patients with no personal history of weight problems experienced the greatest initial weight increase. CONCLUSION: Strategies should be devised to help patients avoid weight gain when starting on VPA, especially if they are not already overweight.

Single and multiple dose pharmacokinetics of enteric coated ketoprofen: effect of cimetidine.

The effect of cimetidine on the single and multiple dose pharmacokinetics of enteric coated ketoprofen was studied in 12 healthy volunteers. Each subject completed two 8-day study treatment periods: either ketoprofen alone (100 mg p.o. twice daily), or co-administered with cimetidine (600 mg twice daily). tlag, Cmax, tmax, t1/2, and k for ketoprofen were not significantly different between single and multiple dose administration. AUC of ketoprofen was slightly but significantly larger following multiple (21.2 micrograms.h.ml-1) as compared to single dose administration (19.0 micrograms.h.ml-1). As a result, plasma clearance of ketoprofen was slightly but significantly reduced following multiple dose administration (80.6 ml/min vs 89.3 ml/min). Cimetidine had no effect on the single or multiple dose pharmacokinetics of enteric coated ketoprofen. Total 12-h urinary recovery of ketoprofen (mostly in the form of ketoprofen glucuronide) was 83.5% of the dose following single dose administration and was significantly greater following multiple dose administration (93.1%). Again cimetidine co-administration had no effect on the single and multiple dose urinary recovery. The results of this study show that cimetidine is not affecting the oral pharmacokinetics of enteric coated ketoprofen.