Methyldopa kinetics before and after ingestion of methyldopa for eight weeks

Abstract

Methyldopa urine and plasma levels and urine metabolite levels were assessed following intravenous (IV) and oral (PO) methyldopa before, and after ingestion of methyldopa (500 mg) daily for eight weeks. There was no increase in (estimated) methyldopa absorption (8.4%) or renal clearance (PO 13.9%, IV 2.33%) after the eight weeks of methyldopa ingestion. However, the initial methyldopa absorption and renal clearance values in this study were higher than that in previous studies. There was an inverse relation between the initial methyldopa absorption and the change in absorption (r - 0.605) and between the initial methyldopa renal clearance and the change in renal clearance (PO r -0.874, IV r -0.891). Overall, this study did not confirm our previous studies showing induction of methyldopa absorption and renal clearance, possibly due to prior up regulation of transporter function. Consistent with methyldopa inducing drug transporters, those with low initial absorption and renal clearance values had the greatest increases.

Evaluation of human intestinal absorption data and subsequent derivation of a quantitative structure–activity relationship (QSAR) with the Abraham descriptors

“…Although this method is better than the urinary recovery method, the intravenous administration of some drugs has not been determined in humans,141,167–232 sometimes because of the low aqueous solubility of the drugs 201. If the drug undergoes extensive hepatic metabolism, the absorption cannot be accurately evaluated by the ratio of urinary excretion of parent drug; this method will under‐estimate the absorption.…”

“…The names of drug and drug‐like compounds and related data are listed in Table 1 and 2. The absorption data was collected and evaluated from 244 papers 1–5, 8–12, 18–251. The following information concerning human drug absorption was recorded from the literature: absorption data given from the literature;oral bioavailability or absolute bioavailability;percentage of cumulative urinary excretion of unchanged drug and its metabolites following oral and intravenous administration;percentage of metabolites in urine or first‐pass effect following oral and intravenous administration;percentage of unchanged drug in urine following oral and intravenous administration;percentage of excretion of drug in bile following oral and intravenous administration;percentage of cumulative excretion of drug in feces following oral and intravenous administration;total recovery of drug in urine and feces following oral and intravenous administration;single dose level in mg or mg/kg and daily oral dose in mg. …”