Abstract
Nine patients taking oral doses of 10 mg/12 h rac-pindolol as part of their treatment for hypertension in pregnancy were recruited for the study. Maternal and fetal gestational age ranged from 20-38 years and 28-41 weeks, respectively. Blood was collected from the umbilical cord vein and from the mother from zero to 12 h after drug administration. Urine was collected for 12 h after rac-pindolol administration at the following intervals: 0-3, 3-6, 6-9, and 9-12 h. Plasma and urine concentrations of the pindolol enantiomers were determined by HPLC using a Chiralpak AD chiral column and fluorescence detection. The data were fitted to a one-compartment model and differences between (+)-R and (-)-S enantiomers were compared by the paired t-test (P < 0.05). Mean results are reported. The disposition of pindolol in maternal plasma was stereoselective, with higher AUC(SS)0-12 (84.34 vs. 95.69 ng.h/ml) and Cl(R) values (9.16 vs. 10.85 L/h) and lower Vd/f (251.38 vs. 225.17 L) and Cl/f (62.48 vs. 55.74 L/h) for the (+)-R pindolol. The transplacental distribution of pindolol was not stereoselective. Cord, plasma, and presumably fetal, concentrations of the pindolol enantiomers were 56% of the maternal plasma concentrations up to 6 h after the last dose.
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