ABSTRACT
OBJECTIVE: Given the lack of data regarding the use of oseltamivir (Tamiflu) during pregnancy, we aimed to evaluate the placental transfer of oseltamivir phosphate and its active metabolite oseltamivir carboxylate, using the perfused placental cotyledon model. STUDY DESIGN: Cotyledons were coperfused with oseltamivir phosphate and oseltamivir carboxylate using the maximal concentrations described with a 75 mg, twice-daily oral dose. Main transfer parameters such as fetal transfer rate (FTR) and clearance index (CI) were assessed. RESULTS: Five placentas were coperfused with oseltamivir phosphate and oseltamivir carboxylate. The median FTR of oseltamivir phosphate was 8.5% (range, 5.0-11.6%) and the median CI was 0.3 (range, 0.2-0.6). Regarding oseltamivir carboxylate transplacental transfer, the median FTR was 6.6% (range, 3.9-9.7%), whereas the median CI was 0.2 (range, 0.2-0.5). CONCLUSION: A transplacental transfer of oseltamivir phosphate and its metabolite oseltamivir carboxylate was detected and might have clinical relevance. Clinicians should be encouraged to report oseltamivir treatment outcomes during pregnancy.
Subject(s)
Antiviral Agents/pharmacokinetics , Maternal-Fetal Exchange , Oseltamivir/pharmacokinetics , Placenta/metabolism , Antiviral Agents/metabolism , Female , Fetus/metabolism , Humans , Oseltamivir/analogs & derivatives , Oseltamivir/metabolism , Pregnancy , Prodrugs/metabolism , Prodrugs/pharmacokineticsABSTRACT
During the 2009 H1N1 influenza pandemics, the concentrations of oseltamivir (O) and its active metabolite (oseltamivir carboxylate [OC]) were determined in 11 children (1 month to 16 years of age) admitted to intensive care units for presumed severe H1N1 infection. They received oseltamivir phosphate (OP) nasogastrically at doses between 1.5 and 6.8 mg/kg of body weight. High OC concentrations were found, with a mean level of 678 ± 535 µg/liter. The mean OP concentration was 27 ± 52 µg/liter. No marked side effect was reported.
Subject(s)
Antiviral Agents/adverse effects , Antiviral Agents/blood , Critical Illness , Oseltamivir/analogs & derivatives , Adolescent , Antiviral Agents/administration & dosage , Antiviral Agents/therapeutic use , Child , Child, Preschool , Female , Humans , Infant , Influenza, Human/drug therapy , Intensive Care Units , Intubation, Gastrointestinal , Male , Oseltamivir/administration & dosage , Oseltamivir/adverse effects , Oseltamivir/blood , Oseltamivir/therapeutic use , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
As the current nutritional zinc intake frequently falls outside the Dietary Reference Intake (DRI) and as zinc is an essential trace mineral involved in the function of many enzymes, zinc supplementation has been recommended to prevent or treat the adverse effects of zinc deficiency. The aim of the present study was to compare the oral bioavailability of zinc bis-glycinate (a new formulation) with zinc gluconate (reference formulation). A randomized, cross-over study was conducted in 12 female volunteers. The two products were administrated orally at the single dose of 15 mg (7.5 mg x 2), with a 7-day wash-out period between the two tests. Serum concentrations of zinc were assayed by a validated inductively coupled plasma optical emission spectrometry (ICP-OES) method and C(max), T(max), and areas-under-the-curve (AUCs) were determined. The comparison between the two treatments was performed by comparing the C(max), AUC(t), and AUC(inf) using an analysis of variance followed by the calculation of the 90% confidence intervals of the ratio test/reference. Bis-glycinate administration was safe and well tolerated and bis-glycinate significantly increased the oral bioavailability of zinc (+43.4%) compared with the gluconate.
