Pharmacokinetic study of methyldopa in aorta-coarctated rats using a microdialysis technique

The pharmacokinetics of methyldopa (12.5, 25 and 50 mg kg(-1), i.p.) was studied in anesthetized sham-operated (SO) and abdominal aorta-coarctated (ACo) rats using a microdialysis technique. A non-linear relationship between the area under the curve (AUC) and dose was observed in SO rats. However, in ACo rats the AUC showed a proportional increase with dose. Abdominal aortic coarctation produced significant differences in the estimates of clearance (Cl) and the elimination rate constant from the dialysate (K(ed)) after the administration of 50 mg kg(-1)of methyldopa (K(ed)SO, 0.31 +/- 0.09; ACo, 0.66 +/- 0.09(*)h(-1): Cl SO, 30.8 +/- 10.1; ACo, 78.6 +/- 13.3(*)mlkg(-1)min(-1);n= 6,(*)P< 0.05 vs SO). In conclusion, this study, by using a microdialysis technique, suggests that abdominal aortic coarctation seems to produce changes in the pharmacokinetics of methyldopa in rats.