DISPOSITION OF MISOPROSTOL AND ITS ACTIVE METABOLITE IN PATIENTS WITHNORMAL AND IMPAIRED RENAL-FUNCTION

The disposition of misoprostol acid, the active metabolite of misopros tol, was studied in 48 subjects with various degrees of renal function after administration of a single 400 mu g oral dose of misoprostol. S ubjects were assigned to one of four treatment groups: group 1, normal renal function with creatinine clearance (CL(CR)) 80-140 mL/min/1.73 m(2); group 2, mild renal impairment with CL(CR) 50-79 mL/min/1.73 m(2 ); group 3, moderate renal impairment with CL(CR) 20-49 mL/min/1.73 m( 2) or group 4, end stage renal disease (ESRD) patients maintained on h emodialysis. The maximum plasma concentration (C-max) and time to reac h C-max (t(max)) for misoprostol acid tended to be larger in group 4 s ubjects; however, it foiled to reach statistical significance, Althoug h not statistically significant, in group 4 subjects the terminal half -life (t(1/2)) Of misoprostol acid was almost twice as large (1.27 +/- 0.77 h) as in groups 1, 2, and 3 (0.70 +/- 0.72, 0.72 +/- 0.67, and 0 .73 +/- 0.45 h, respectively), Misoprostol acid's total area under the plasma concentration curve (AUC(0)(infinity)) was larger in group 4 s ubjects (1173.5 +/- 487.4 pg . h/mL) as compared with groups 1,2, and 3 (421.4 +/- 263.1, 418.9 +/- 114.5, and 377.0 +/- 145.2 pg . h/mL, re spectively; P < .05). The apparent total body clearance (CL) of misopr ostol acid was statistically significantly smaller in group 4 subjects (0.094 +/- 0.044 L/kg/min) as compared only with group 3 subjects (0. 284 +/- 0.102 L/kg/min). The dose of misoprostol may need to be reduce d in ESRD patients on prolonged hemodialysis to prevent unnecessary hi gh plasma levels of misoprostol acid and to avoid possible dose-relate d adverse effects.