A. Skerjanec et al., PHARMACOKINETICS AND PRESYSTEMIC GUT METABOLISM OF METHYLDOPA IN HEALTHY-HUMAN SUBJECTS, Journal of clinical pharmacology, 35(3), 1995, pp. 275-280
This study examined the pharmacokinetics and metabolism of methyldopa
after giving single 250-mg oral and intravenous doses to 16 healthy hu
man volunteers. A 48-hour washout period was allowed between oral and
intravenous treatments. Blood and urine samples were collected; methyl
dopa was assayed in blood and urine, and its metabolites (methyldopa s
ulfate, alpha-methyldopamine, and alpha-methyldopamine sulfate) were a
ssayed in urine. Pharmacokinetic parameters were recorded as follows:
half-life was 2.0 +/- 0.7 hours; total body and renal clearance were 2
68 +/- 72 and 107 +/- 35 mL/min, respectively; and volume of distribut
ion at steady-state was 33 +/- 11 L. The absolute bioavailability of t
he drug was 42 +/- 16%. The measurable metabolites in urine after oral
and intravenous administration accounted for 27% and 17% of the dose,
respectively. Methyldopa sulfate was the most abundant metabolite rec
orded; its quantity was higher after oral than after intravenous admin
istration, 20.1 +/- 5.7% versus 6.7 +/- 5.3% of the dose (P < .05), su
ggesting significant presystemic gut metabolism. First-pass gut metabo
lism for methyldopa was estimated to be 17.6 +/- 6.9% of the dose give
n.