SINGLE-DOSE PHARMACOKINETICS OF FELBAMATE IN PATIENTS WITH RENAL DYSFUNCTION

Aims The purpose of this study was to evaluate the effects of renal im pairment on the single-dose pharmacokinetics of the antiepileptic felb amate. Methods Twelve subjects with three levels of renal dysfunction (creatinine clearance > 30-80, > 10-30 or 5-10 m min(-1)) and four con trols with normal renal function (creatinine clearance > 80 mi min(-1) were studied). Plasma and urine samples were obtained for 144 h follo wing administration of a single 1200 mg dose. Results Compared with co ntrols, apparent total body clearance, renal clearance and urinary exc retion of felbamate were decreased, and half-life, C-max and AUC value s were increased in subjects with renal dysfunction. The magnitude of these changes was associated with the degree of renal dysfunction. Non renal clearance and apparent volume of distribution values were also l ower in renal dysfunction subjects, but there was no association betwe en the extent of these changes and degree of renal dysfunction. Renal clearance of felbamate accounted for approximately 30% of apparent tot al body clearance in the control group and from 9-22% in the renal fai lure patients. Renal clearance of felbamate was significantly correlat ed with creatinine clearance (r(2) = 0.75; P < 0.001). Conclusions The se data suggest that initial dosage and titration of felbamate may req uire adjustment in patients with renal dysfunction.