Pharmacokinetics of oseltamivir according to trimester of pregnancy

Abstract

Objective To determine pharmacokinetic parameters for oseltamivir in all trimesters of pregnancy. Methods Thirty pregnant women, 10 per trimester, receiving oseltamivir phosphate 75 mg were recruited to study first-dose pharmacokinetics. Plasma samples were obtained at 0, 0.5, 1, 2, 4, 8, and 12 hours after the first dose. Samples were analyzed for oseltamivir and oseltamivir carboxylate levels. Using a noncompartmental model, area-under-the-curve (AUC), maximum concentration (Cmax), time-to-maximum concentration (Tmax), and half-life (T1/2) were estimated. Results There were no significant differences in the pharmacokinetics of oseltamivir by trimester except for an increased T1/2 in the first trimester for oseltamivir phosphate and an increased Cmax in the third trimester for oseltamivir carboxylate. The levels of oseltamivir carboxylate observed were within the range needed to achieve IC50 concentrations for pandemic H1N1. Conclusion The pharmacokinetics of oseltamivir do not change significantly according to trimester of pregnancy.

Pandemic Influenza A (H1N1) Infection in Pregnant and Nonpregnant Women in Spain (2009–2010)

“…Probably, early identification and treatment were the most important factors in the evolution of illness in both the groups of patients. Most authors recommend oseltamivir as the preferred treatment for pregnant women (11,(21)(22)(23), and this was the antiviral of choice for most cases in our study.…”

“…During the pandemic (20), experts debated the most appropriate treatments for use in pregnancy; however, limited data were available at that time (21)(22)(23).…”

Influenza

“…The CDC recommends the same dose of oseltamivir (75 mg twice daily for 5 days) for pregnant women as for nonpregnant patients, with pharmacokinetic studies demonstrating levels that remain constant across trimesters of pregnancy. 13 A higher Duryea & Sheffield dose has been recommended by some (150 mg twice a day) in immunocompromised and severely ill patients, although limited data suggest that higher dosing may not provide additional benefit. Extended treatment may be warranted in severe cases and decision for treatment should be guided by virologic polymerase chain reaction testing.…”

Grippe et grossesse

“…L'oseltamivir est une pro-drogue nécessitant une hydrolyse hépatique pour libérer son métabolite actif, l'oseltamivir carboxylate, dont la demi-vie d'élimination est d'environ 6 à 10 heures. Les paramètres pharmacocinétiques ne sont pas significativement altérés pendant la grossesse [31,32]. Des expériences pratiquées sur des explants placentaires suggèrent un métabolisme placentaire important, avec une accumulation minimale du métabolite actif sur le versant placentaire lors d'expositions placentaires au moins 20 fois supérieures aux taux thérapeutiques usuels [33].…”