Papini Olga, Mathes Angelo Carmo Silva, Cunha Sergio Pereira Da, Lanchote Vera Lucia
Faculadade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
Chirality. 2004 Feb;16(2):65-71. 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(R) 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 V(d/f) (140.60 vs. 132.81 L for group A and 197.86 vs. 169.46 L for group B) and C(l/f) (29.00 vs. 25.43 L/h for group A and 33.15 vs. 26.39 L/h for group B) and lower t(1/2)beta (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 V(d/f) (197.86 vs. 140.60 L for (+)-(R) and 169.46 vs. 132.81 L for (-)-(S)) and t(1/2)beta 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.
本研究的目的是调查布比卡因在足月产妇分娩期间的动力学处置和经胎盘分布中的立体选择性。产妇年龄在18 - 37岁之间，胎儿胎龄在37.6 - 41.5周之间。健康产妇（n = 23）单独接受硬膜外0.5%消旋布比卡因（A组）或与肾上腺素联合使用（B组）。在给药后8小时内定期采集产妇静脉血，并在分娩时采集脐静脉血。使用Chiralcel® OD - R柱和紫外检测器通过高效液相色谱法测定血浆样品中的布比卡因对映体。将一室或二室模型拟合到数据中，并使用配对Wilcoxon检验比较（+）-（R）和（-）-（S）对映体之间的差异（P < 0.05）。使用未配对Mann - Whitney检验评估肾上腺素的影响（P < 0.05）。布比卡因在产妇血浆中的处置具有立体选择性，对于（+）-（R）-布比卡因，观察到更高的V（d/f）（A组为140.60对132.81 L，B组为197.86对169.46 L）和C（l/f）（A组为29.00对25.43 L/h，B组为33.15对26.39 L/h）以及更低的t（1/2）β（A组为3.24对3.30 h，B组为4.36对4.45 h）。肾上腺素的联合给药导致更高的V（d/f）（（+）-（R）为197.86对140.60 L，（-）-（S）为169.46对132.81 L）和t（1/2）β值（（+）-（R）为4.36对3.24 h，（-）-（S）为4.45对3.30 h）。仅当布比卡因在不使用肾上腺素的情况下给药时（B组），布比卡因的经胎盘分布才具有立体选择性，观察到（-）-（S）-布比卡因的脐血/母血比值更高（0.40对0.35）。《手性》16:65 - 71，2004年。
