Total, Unbound, Renal, and Hepatic Clearances of Raltegravir and the Formation and Elimination Clearances of Raltegravir Glucuronide in Pregnant Women

Autor(es)

Moreira, Fernanda de Lima ; Paz, Tiago Antunes ; Melli, Patricia Pereira dos Santos ; Thomaz, Matheus de Lucca ; Marques, Maria Paula ; Rocha, Adriana ; Duarte, Geraldo ; Lanchote, Vera Lucia

• Tipo de documento: Artigo Científico
• Fonte: Journal of Clinical Pharmacology; v. N/A, p. 8-pg., 2023-06-20.

Resumo

This 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 & PRIME; 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. (AU)

• Processo FAPESP: 16/23938-2 - Influência da gravidez associada com HIV na atividade do transportador OATP em pacientes em tratamento com Efavirenz
• Beneficiário: Fernanda de Lima Moreira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/05616-3 - Farmacocinética clínica em doenças infecciosas
• Beneficiário: Vera Lúcia Lanchote
• Modalidade de apoio: Auxílio à Pesquisa - Temático