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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Pharmacokinetics and Placental Transfer of Bupivacaine Enantiomers in HIV-Infected Parturient Women on Antiretroviral Therapy

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Oliveira Souza, Marilia Cristina [1] ; Marques, Maria Paula [1] ; Duarte, Geraldo [2] ; Lanchote, Vera Lucia [1]
Total Authors: 4
[1] Univ Sao Paulo, Dept Clin Toxicol & Bromatol Anal, Sch Pharmaceut Sci Ribeirao Preto, Sao Paulo - Brazil
[2] Univ Sao Paulo, Dept Gynecol & Obstet, Ribeirao Preto Med Sch, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Journal of Clinical Pharmacology; v. 60, n. 5 NOV 2019.
Web of Science Citations: 0

Bupivacaine, a local anesthetic, is commercialized as a racemic mixture of R-bupivacaine and S-bupivacaine enantiomers. HIV infection increases the expression of placental P-glycoprotein (P-gp), and antiretroviral (ARV) therapy inhibits cytochrome P450 3A and P-gp. The present study evaluates the kinetic disposition of bupivacaine enantiomers in HIV-infected parturient women on ARV therapy. In this study, HIV-infected parturient women (n = 10) treated with zidovudine, lamivudine, lopinavir, and ritonavir were investigated. Anesthesia and/or analgesia was achieved by the administration of 0.5% racemic bupivacaine hydrochloride with 1:200000 epinephrine in the epidural space at doses of 2.5 to 22.5 mg. Maternal serial blood samples were obtained at the time immediately before and 5, 15, 30, 45, and 60 minutes and 2, 4, 6, 8, 10, 12, and 14 hours after administration of the bupivacaine. At the time of delivery, samples of maternal and umbilical cord vein blood were also collected. The results suggest that bupivacaine pharmacokinetics are enantioselective, revealing higher maternal plasma concentrations of the R-bupivacaine enantiomer (area under the total plasma concentration-time curve was calculated by the trapezoid method with extrapolation to infinity/dose((S)/(R)) = 0.91; P < .05). The plasma unbound fraction of the drug (0.09 vs 0.06) and the umbilical cord vein/maternal plasma ratio (0.47 vs 0.39) were higher for the R-bupivacaine enantiomer than the S-bupivacaine enantiomer (P < .05). ARV therapy with ritonavir confers an enantioselective interaction between the enantiomers of bupivacaine and placental P-gp, producing greater inhibition of efflux transport of the R-bupivacaine enantiomer. Possible changes in the well-being of the fetuses of mothers under analgesia may be a consequence of the increased placental transfer of bupivacaine enantiomers to the fetal circulation. (AU)

FAPESP's process: 13/06708-5 - Kinetic disposition and placental transfer of bupivacaine enantiomers in HIV-infected pregnant women in antiretroviral therapy.
Grantee:Marília Cristina Oliveira Souza
Support type: Scholarships in Brazil - Master