Stereoselectivity in the placental transfer and kinetic disposition of racemic bupivacaine administered to parturients with or without a vasoconstrictor

• Published in: Chirality (New York, N.Y.) N.Y.), 2004, Vol.16 (2), p.65-71
• Main Authors: Papini, Olga, Do Carmo Silva Mathes, Ângelo, Pereira Da Cunha, Sergio, Lucia Lanchote, Vera
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; bupivacaine; Bupivacaine - administration & dosage; Bupivacaine - blood; Bupivacaine - chemistry; Bupivacaine - pharmacokinetics; enantiomers; Epinephrine - administration & dosage; Epinephrine - pharmacology; Female; Fetal Blood - drug effects; Fetal Blood - metabolism; Humans; Kinetics; Maternal Age; Maternal-Fetal Exchange - drug effects; parturients; Parturition - physiology; pharmacokinetics; placental transfer; Pregnancy; Stereoisomerism; Vasoconstrictor Agents - administration & dosage; Vasoconstrictor Agents - pharmacology
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.10308

The aim of the present study was to investigate the stereoselectivity in the kinetic disposition and the transplacental distribution of bupivacaine in term parturients during labor. Maternal age ranged from 18–37 years and fetal gestational age from 37.6–41.5 weeks. Healthy parturients (n = 23) received epidural 0.5% racemic bupivacaine alone (group A) or combined with epinephrine (group B). Maternal venous blood was sampled at regular intervals until 8 h after drug administration and umbilical venous blood was obtained at delivery. Bupivacaine enantiomers were determined in plasma samples by HPLC using a Chiralcel® OD‐R column and a UV detector. One‐ or two‐compartment models were fitted to data and differences between the (+)‐(R) and (–)‐(S) enantiomers were compared with the paired Wilcoxon test (P< 0.05). The influence of epinephrine was evaluated using the unpaired Mann‐Whitney test (P< 0.05). The disposition of bupivacaine in maternal plasma was stereoselective, with higher Vd/f (140.60 vs. 132.81 L for group A and 197.86 vs. 169.46 L for group B) and Cl/f (29.00 vs. 25.43 L/h for group A and 33.15 vs. 26.39 L/h for group B) and lower t1/2β (3.24 vs. 3.30 h for group A and 4.36 vs. 4.45 h for group B) being observed for (+)‐(R)‐bupivacaine. The combined administration of epinephrine resulted in higher Vd/f (197.86 vs. 140.60 L for (+)‐(R) and 169.46 vs. 132.81 L for (–)‐(S)) and t1/2β values (4.36 vs. 3.24 h for (+)‐(R) and 4.45 vs. 3.30 h for (–)‐(S)). The transplacental distribution of bupivacaine was stereoselective only when bupivacaine was administered without epinephrine (group B), with a higher cord blood/maternal blood ratio being observed for (–)‐(S)‐bupivacaine (0.40 vs. 0.35). Chirality 16:65–71, 2004. © 2004 Wiley‐Liss, Inc.