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Enantioselectivity in the steady‐state pharmacokinetics and transplacental distribution of pindolol at delivery in pregnancy‐induced hypertension
Author(s) -
Gonçalves Paulo Vinicius Bernardes,
Matthes Ângelo Do Carmo Silva,
Da Cunha Sérgio Pereira,
Lanchote Vera Lucia
Publication year - 2002
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.10124
Subject(s) - pindolol , chemistry , pharmacokinetics , transplacental , enantiomer , stereoselectivity , umbilical cord , high performance liquid chromatography , urine , pharmacology , fetus , endocrinology , chromatography , medicine , pregnancy , stereochemistry , biochemistry , placenta , receptor , biology , genetics , catalysis , anatomy
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. Chirality 14:683–687, 2002. © 2002 Wiley‐Liss, Inc.