THE EFFECT OF RENAL-DISEASE ON THE DISPOSITION OF VENLAFAXINE

The pharmacokinetics of venlafaxine and its active metabolite O-desmet hylvenlafaxine were studied in subjects with various degrees of renal dysfunction, including subjects requiring maintenance hemodialysis. Ve nlafaxine was administered as a single 50 mg dose, with blood and urin e samples obtained at intervals up to 48 hours after administration fo r the subjects receiving dialysis or 72 hours for the subjects not rec eiving dialysis. Six subjects receiving dialysis also completed an int radialysis evaluation to estimate dialysis clearance. Concentrations o f venlafaxine and O-desmethylvenlafaxine in plasma, urine, and dialysa te fluid were determined by high-performance liquid chromatography. Ap parent total clearance of venlafaxine and O-desmethylvenlafaxine were both significantly decreased by approximately 55% in the subjects rece iving dialysis, and terminal disposition half-life was significantly p rolonged for both compounds. Venlafaxine and O-desmethylvenlafaxine ar e poorly dialyzable. In conclusion, the disposition of venlafaxine and O-desmethylvenlafaxine is markedly altered in renal disease; therefor e dosage adjustment is warranted for patients with creatinine clearanc e values below 30 ml/min.