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The IUPHAR/BPS Guide to PHARMACOLOGY in 2018: updates and expansion to encompass the new guide to IMMUNOPHARMACOLOGY.2018 年 IUPHAR/BPS 药理学指南:更新和扩展,以包含新的免疫药理学指南。
Nucleic Acids Res. 2018 Jan 4;46(D1):D1091-D1106. doi: 10.1093/nar/gkx1121.
2
THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Transporters.2017/18 年药理学简明指南:转运蛋白。
Br J Pharmacol. 2017 Dec;174 Suppl 1(Suppl Suppl 1):S360-S446. doi: 10.1111/bph.13883.
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THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Enzymes.《药理学简明指南 2017/18:酶》
Br J Pharmacol. 2017 Dec;174 Suppl 1(Suppl Suppl 1):S272-S359. doi: 10.1111/bph.13877.
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Placental control of drug delivery.胎盘对药物递送的控制。
Adv Drug Deliv Rev. 2017 Jul 1;116:63-72. doi: 10.1016/j.addr.2016.08.002. Epub 2016 Aug 12.
5
Pregnancy-related pharmacokinetic changes.与妊娠相关的药代动力学变化。
Clin Pharmacol Ther. 2016 Jul;100(1):53-62. doi: 10.1002/cpt.382. Epub 2016 May 14.
6
An integrated pharmacokinetic model for the influence of CYP3A4 expression on the in vivo disposition of lopinavir and its modulation by ritonavir.CYP3A4 表达对洛匹那韦体内处置的影响及其被利托那韦调制的综合药代动力学模型。
J Pharm Sci. 2011 Jun;100(6):2508-15. doi: 10.1002/jps.22457. Epub 2010 Dec 29.
7
Effects of a P-glycoprotein modulator on the pharmacokinetics and distribution of free levobupivacaine and bupivacaine in rats.P-糖蛋白调节剂对游离左布比卡因和布比卡因在大鼠体内药代动力学和分布的影响。
Int J Pharm. 2010 Aug 30;396(1-2):127-33. doi: 10.1016/j.ijpharm.2010.06.038. Epub 2010 Jun 25.
8
Effects of cytochrome P450 3A (CYP3A) and the drug transporters P-glycoprotein (MDR1/ABCB1) and MRP2 (ABCC2) on the pharmacokinetics of lopinavir.细胞色素 P450 3A(CYP3A)以及药物转运蛋白 P-糖蛋白(MDR1/ABCB1)和多药耐药相关蛋白 2(MRP2/ABCC2)对洛匹那韦药代动力学的影响。
Br J Pharmacol. 2010 Jul;160(5):1224-33. doi: 10.1111/j.1476-5381.2010.00759.x.
9
Distribution of bupivacaine enantiomers and lidocaine and its metabolite in the placental intervillous space and in the different maternal and fetal compartments in term pregnant women.布比卡因对映体和利多卡因及其代谢物在足月孕妇胎盘绒毛间隙及不同母胎隔室中的分布。
J Clin Pharmacol. 2011 Feb;51(2):212-7. doi: 10.1177/0091270010365551. Epub 2010 Apr 16.
10
Functional role of p-glycoprotein and binding protein effect on the placental transfer of lopinavir/ritonavir in the ex vivo human perfusion model.P-糖蛋白的功能作用及结合蛋白对洛匹那韦/利托那韦在离体人灌注模型中胎盘转运的影响
Obstet Gynecol Int. 2009;2009:726593. doi: 10.1155/2009/726593. Epub 2009 May 18.

洛匹那韦/利托那韦治疗增加了人类免疫缺陷病毒感染孕妇布比卡因对映体向胎盘的转移。

Lopinavir/ritonavir treatment increases the placental transfer of bupivacaine enantiomers in human immunodeficiency virus-infected pregnant women.

机构信息

Department of Obstetrics and Gynecology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

Department of Clinical Analysis, Food Science and Toxicology, School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

出版信息

Br J Clin Pharmacol. 2018 Oct;84(10):2415-2421. doi: 10.1111/bcp.13700. Epub 2018 Aug 2.

DOI:10.1111/bcp.13700
PMID:29959798
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6138485/
Abstract

AIMS

The present study evaluated the placental transfer and amniotic fluid distribution of bupivacaine enantiomers in health pregnant women and in human immunodeficiency virus (HIV)-infected pregnant women receiving epidural anaesthesia for caesarean section.

METHODS

Twelve HIV-infected pregnant women (HIV group) were treated long-term (at least 8 weeks) with lopinavir/ritonavir (400/100 mg twice daily), and 12 healthy pregnant women (Control group) who submitted to epidural anaesthesia with racemic bupivacaine (75 mg) during caesarean section were investigated. At delivery, samples of maternal and fetal blood and amniotic fluid were collected (10-20 min after drug administration).

RESULTS

The placental transfer ratio of bupivacaine enantiomers was significantly higher among the pregnant women from the HIV group when compared with those from the Control group (Mann-Whitney test, P ≤ 0.05). Placental transfer ratios (median and 25th - 75th percentiles) for (+)-(R)-bupivacaine were 0.58 (0.38-0.82) in the HIV group vs. 0.25 (0.18-0.33) in the Control group, and for (-)-(S)-bupivacaine, they were 0.54 (0.34-0.69) in the HIV group vs. 0.25 (0.19-0.29) in the Control group. The transplacental distribution of bupivacaine was stereoselective only in the HIV group. The umbilical artery/umbilical vein ratio and amniotic fluid/maternal vein ratio were low and nonstereoselective, and no statistically significant differences were observed between the groups.

CONCLUSIONS

This study supports that the placental transfer of both bupivacaine enantiomers was 100% higher in HIV-pregnant women treated with lopinavir/ritonavir when compared with that in healthy pregnant women receiving epidural anaesthesia for caesarean section.

摘要

目的

本研究评估了健康孕妇和接受剖宫产术硬膜外麻醉的人类免疫缺陷病毒(HIV)感染孕妇中布比卡因对映体的胎盘转运和羊水中分布。

方法

12 名 HIV 感染孕妇(HIV 组)长期(至少 8 周)接受洛匹那韦/利托那韦(400/100mg,每日两次)治疗,12 名健康孕妇(对照组)在剖宫产时接受布比卡因(75mg)硬膜外麻醉,收集分娩时产妇和胎儿的血液和羊水样本(给药后 10-20 分钟)。

结果

与对照组相比,HIV 组孕妇布比卡因对映体的胎盘转运率明显更高(Mann-Whitney 检验,P≤0.05)。HIV 组中(+)-(R)-布比卡因的胎盘转运率中位数(25%-75%分位数)为 0.58(0.38-0.82),对照组为 0.25(0.18-0.33),(-)-(S)-布比卡因分别为 0.54(0.34-0.69)和 0.25(0.19-0.29)。仅在 HIV 组中,布比卡因的胎盘分布具有立体选择性。脐动脉/脐静脉比值和羊水/母血比值均较低,且无立体选择性,两组间无统计学差异。

结论

本研究表明,与接受剖宫产术硬膜外麻醉的健康孕妇相比,接受洛匹那韦/利托那韦治疗的 HIV 孕妇中布比卡因两种对映体的胎盘转运率均增加了 100%。