Affiliation:
1. Department of Clinical Analysis, Food Science and Toxicology School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo Ribeirão Preto São Paulo Brazil
2. Faculty of Pharmacy Federal University of Rio de Janeiro Rio de Janeiro Brazil
3. Department of Gynecology and Obstetrics, Ribeirão Preto Medical School University of São Paulo Ribeirão Preto São Paulo Brazil
Abstract
AbstractThis work aimed to evaluate the total, unbound, renal, and hepatic clearances of raltegravir (RAL) and the formation and elimination clearances of raltegravir glucuronide (RAL GLU) in pregnant women living with HIV. The participants received RAL 400 mg twice daily during the third trimester (n = 15) of gestation, delivery (n = 15), and the postpartum period (n = 8). Pharmacokinetic parameter values were calculated on the basis of plasma and urine data using noncompartmental methods. RAL clearances for the third trimester of gestation were as follows: total clearance: geometric mean, 63.63 L/h (95% CI, 47.5–85.25); renal clearance: geometric mean, 2.56 L/h (95% CI, 1.96–3.34); hepatic clearance: geometric mean, 60.52 L/h (95% CI, 44.65–82.04); and unbound clearance: geometric mean, 281.14 L/h (95% CI, 203.68–388.05). RAL GLU formation and elimination clearances for the third trimester of gestation were 7.57 L/h (95% CI, 4.94–11.6) and 8.71 L/h (95% CI, 6.71‐11.32), respectively. No differences were observed in RAL GLU pharmacokinetic parameters between the third trimester of gestation and the postpartum period, except for higher formation (7.57 vs 4.03 L/h) and elimination (8.71 vs 4.92 L/h) clearances during the third trimester. The findings based on plasma and urine data are consistent with an increase in the hepatic uridine 5′ diphospho‐glucuronosyltransferase isoenzymes activities involved in RAL metabolism during pregnancy, and the formation of RAL GLU is a minor route of RAL elimination. Compared to the postpartum period, in the third trimester of gestation, the similar RAL plasma exposure in pregnant women reinforces the maintenance of an RAL regimen including a 400‐mg oral dose twice daily during pregnancy.
Subject
Pharmacology (medical),Pharmacology
Reference26 articles.
1. WHO.Mother‐to‐child transmission of HIV.https://www.who.int/teams/global‐hiv‐hepatitis‐and‐stis‐programmes/hiv/prevention/mother‐to‐child‐transmission‐of‐hiv
2. Panel on Treatment of HIV‐Infected Pregnant Women and Prevention of Perinatal Transmission. HIV‐1‐Infected women for maternal health and interventions to recommendations for use of antiretroviral drugs in pregnant HIV‐1‐Infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States;2020.https://clinicalinfo.hiv.gov/en/guidelines/perinatal/overview.
3. ArribasJ MarzoliniC MallonP et al.European AIDS Clinical Society (EACS) Guidelines.European AIDS Society (EACS);2021.
4. Ministério da Saúde do Brasil.Protocolo clínico e diretrizes terapêuticas para prevenção da transmissão vertical de/ hiv sífilis e hepatites virais.https://www.gov.br/aids/pt‐br/centrais‐de‐conteudo/pcdts/2022/hiv‐sifilis‐e‐hepatites‐virais/pcdt_tv_internet_13‐06‐22‐2.pdf
5. Raltegravir versus efavirenz in antiretroviral-naive pregnant women living with HIV (NICHD P1081): an open-label, randomised, controlled, phase 4 trial