title: Pharmacokinetics and presystemic gut metabolism of methyldopa in healthy human subjects.
abstract: This study examined the pharmacokinetics and metabolism of methyldopa after giving single 250-mg oral and intravenous doses to 16 healthy human volunteers. A 48-hour washout period was allowed between oral and intravenous treatments. Blood and urine samples were collected; methyldopa was assayed in blood and urine, and its metabolites (methyldopa sulfate, alpha-methyldopamine, and alpha-methyldopamine sulfate) were assayed in urine. Pharmacokinetic parameters were recorded as follows: half-life was 2.0 +/- 0.7 hours; total body and renal clearance were 268 +/- 72 and 107 +/- 35 mL/min, respectively; and volume of distribution at steady-state was 33 +/- 11 L. The absolute bioavailability of the 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 recorded; its quantity was higher after oral than after intravenous administration, 20.1 +/- 5.7% versus 6.7 +/- 5.3% of the dose (P < .05), suggesting significant presystemic gut metabolism. First-pass gut metabolism for methyldopa was estimated to be 17.6 +/- 6.9% of the dose given.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Skerjanec
authors.forename: N R
authors.initials: NR
authors.lastname: Campbell
authors.forename: S
authors.initials: S
authors.lastname: Robertson
authors.forename: Y K
authors.initials: YK
authors.lastname: Tam
mesh_terms: D000284:Administration, Oral; D000328:Adult; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008750:Methyldopa / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics*
chemical_list: D008750:Methyldopa