PT - JOURNAL ARTICLE AU - K C Kwan AU - E L Foltz AU - G O Breault AU - J E Baer AU - J A Totaro TI - Pharmacokinetics of methyldopa in man. DP - 1976 Aug 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 264--277 VI - 198 IP - 2 4099 - http://jpet.aspetjournals.org/content/198/2/264.short 4100 - http://jpet.aspetjournals.org/content/198/2/264.full SO - J Pharmacol Exp Ther1976 Aug 01; 198 AB - Single doses of methyldopa were administered orally and intravenously as aqueous solutions to 12 healthy volunteers in a crossover study. Serial plasma and urine samples were analyzed specifically for methyldopa and its O-sulfate conjugate. Kinetic analyses of the results indicated that methyldopa disposition could be adequately represented by a two-compartment open model. Renal excretion accounted for about two-thirds of the plasma clearance of methylodopa. Absorption profiles were constructed with the aid of the pharmacokinetic model and contrasted with estimates of absorption which were model-independent. The mean fraction reaching the systemic circulation as methyldopa was estimated to be 0.25 (range 0.08-0.62 for n = 11). Although most of the absorption occurred within the first 5 hours oral administration, a minor component, suggestive of limited enterohepatic circulation, persisted from 9 to 36 hours. O-sulfate conjugation was route-dependent and appeared to be derived predominantly, if not exclusively, as a first-pass effect of absorption and/or enterophepatic circulation.