Pharmacokinetics of methyldopa in man.
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.
D000284:Administration, Oral; D001702:Biopharmaceutics; D002986:Clinical Trials as Topic; D004764:Enterohepatic Circulation; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D008750:Methyldopa / Q000008:administration & dosage / Q000378:metabolism*; D008954:Models, Biological; D013997:Time Factors
D008750:Methyldopa