Objective
Women in the postpartum period are at high risk for complications from influenza. Pharmacokinetic data of oseltamivir phosphate in postpartum women, however, are lacking.
Study Design
Seven healthy patients within 48 hours of delivery were recruited. Each woman received 75 mg of oseltamivir phosphate. Plasma and breast milk samples were obtained at times 0, 0.5, 1, 2, 4, 8, 12, and 24 hours after the first dose. The samples were analyzed for oseltamivir and oseltamivir carboxylate levels. Using a noncompartmental model, area under the curve (AUC), maximum concentration (C max ), time to maximum concentration, and half-life were estimated.
Results
Oseltamivir phosphate and oseltamivir carboxylate were found in breast milk, although later and in lower levels than that found in plasma. The C max and AUC 0-24 was higher for the active metabolite than for the prodrug in both plasma and breast milk.
Conclusion
Oseltamivir carboxylate was present in breast milk but in concentrations significantly lower than considered therapeutic in infants.
Increased morbidity and mortality from influenza in pregnancy have been reported for seasonal and pandemic influenza. The 2009 H1N1 pandemic demonstrated that pregnant women are a high-risk group with increased rates of hospital admission, intensive care admission, and death. This high-risk status extends to women in the postpartum period. Although it is difficult to say at what time period postpartum a woman’s immune system returns to the nonpregnant status, the Centers for Disease Control and Prevention identified women up to 2 weeks postpartum as being at increased risk of complications of H1N1 and recommended prompt initiation of antiviral treatment with oseltamivir.
Oseltamivir is a neuraminidase inhibitor that is effective against both influenza A and influenza B that works by blocking progeny virion release. It has been shown to reduce the duration of viral replication, the severity and duration of influenza symptoms, the levels of biochemical markers of host inflammatory response, and the incidence of secondary infections. There are no published studies addressing dosing during the postpartum period. Moreover, the only human data regarding the transfer of oseltamivir or its active metabolite into breast milk is a published journal correspondence. To provide some guidance on these issues, we studied the pharmacokinetics of the first dose oseltamivir in women in the immediate postpartum time period.
Materials and Methods
This study was approved by the Internal Review Board at the University of Texas Southwestern Medical Center (Dallas, TX). The study was performed at Parkland Memorial Hospital from March 2010 to May 2010 by the Departments of Obstetrics and Gynecology and Pediatrics at University of Texas Southwestern and in conjunction with the Pediatric Pharmacology Research Unit Network.
Patients’ age of 18 years and older without other medical problems following an uncomplicated delivery of a singleton gestation and who had elected to exclusively bottle feed their infants were eligible for the study. Patients were excluded if their delivery was complicated by chorioamnionitis, metritis, or postpartum hemorrhage. Patients were also excluded if they had an allergy or prior adverse reaction to oseltamivir or known kidney or liver disease.
Patients who consented to participate in the study received a single 75 mg capsule of oseltamivir phosphate (Tamiflu; Roche, Nutley, NJ). They had blood and breast milk samples collected the time of the first dose of medication and at 0.5, 1, 2, 4, 8, 12, and 24 hours after the single dose of oseltamivir. Blood samples were processed to separate plasma, and plasma and breast milk samples were stored at –80°C for batch analysis.
Plasma and breast milk samples were shipped to BASI Laboratory (Kenilworth, UK) and analyzed for oseltamivir phosphate and oseltamivir carboxylate content using a validated tandem mass spectrometric method (method on file). The method was accurate and sensitive ranging from 1 to 10 ng/mL (relative SD <5%) for oseltamivir phosphate and oseltamivir carboxylate, respectively.
Oseltamivir and oseltamivir carboxylate concentrations (nanograms per milliliter) in plasma and breast milk were plotted vs time (hours) for each of the respective subjects. Using a noncompartmental model, area under the curve (AUC), maximum concentration (C max ), time to maximum concentration (T max ), and half-life (T ½ ) were estimated using Thermo Kinetica 5.0 (Thermo Fischer Scientific, Waltham, MA). The pharmacokinetic estimates were summarized. An analysis of variance and Ryan-Einot-Gabriel-Welsh multiple range test were used to determine significance between study variables (SAS 9.2; SAS Institute, Cary, NC).
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
