PHARMACOKINETICS OF METHYLDOPA IN MAN

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  • 1 January 1976
    • journal article
    • research article
    • Vol. 198  (2) , 264-277
Abstract
Single doses of methyldopa [an effective antihypertensive agent] were administered orally and i.v. 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 2-compartment open model. Renal excretion accounted for about 2/3 of the plasma clearance of methyldopa. 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 h after oral administration, a minor component, suggestive of limited enterohepatic circulation, persisted from 9 to 36 h. O-sulfate conjugation was route-dependent and appeared to be derived predominantly, if not exclusively, as a 1st-pass effect of absorption and/or enterohepatic circulation.