METHYLDOPA KINETICS BEFORE AND AFTER INGESTION OF METHYLDOPA FOR 8 WEEKS

Methyldopa urine and plasma levels and urine metabolite levels were as sessed following intravenous (IV) and oral(PO) methyldopa before, and after ingestion of methyldopa (500 mg) daily for eight weeks. There wa s no increase in (estimated) methyldopa absorption (8.4%) or renal cle arance (PO 13.9%, IV 2.33%) after the eight weeks of methyldopa ingest ion. However, the initial methyldopa absorption and renal clearance va lues in this study were higher than in previous studies. There was an inverse relation between the initial methyldopa absorption and the cha nge in absorption (r - 0.605) and between the initial methyldopa renal clearance and the change in renal clearance (PO r - 0.874, IV r - 0.8 91). Overall, this study did not confirm our previous studies showing induction of methyldopa absorption and renal clearance, possibly due t o prior up regulation of transporter function. Consistent with methyld opa inducing drug transporters, those with low initial absorption and renal clearance values had the greatest increases.