We sought to delineate the pharmacokinetics (PK) of oseltamivir and its active metabolite oseltamivir carboxylate during pregnancy. Physiologic changes of pregnancy, including increased renal filtration and secretion, may increase the clearance of oseltamivir carboxylate. Sixteen pregnant women taking oseltamivir for prophylaxis or treatment of suspected/proven influenza infection were enrolled. Twenty-three nonpregnant reproductive-age females served as the control group. The primary PK endpoint was area under the plasma concentration time curve for oseltamivir carboxylate. Pregnancy did not alter the PK parameters of the parent compound, oseltamivir. However, for oseltamivir carboxylate the area under the plasma concentration time curve was significantly lower (P = .007) and the apparent clearance significantly higher (P = .006) in pregnant women compared with nonpregnant women. Pregnancy produces lower systemic levels of oseltamivir carboxylate. Increasing the dose and/or dosing frequency of oseltamivir during pregnancy may be necessary to achieve comparable exposure in pregnant and nonpregnant women.
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http://dx.doi.org/10.1016/j.ajog.2011.03.002 | DOI Listing |
Antiviral Res
December 2024
Department of Biochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka-shi, Shizuoka, 422-8526, Japan.
Sci Total Environ
November 2024
Department of Pharmacy, Osaka Medical and Pharmaceutical University, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan.
ACS Cent Sci
August 2024
Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 08826, Republic of Korea.
We present orally administrable prodrugs (s) of guanidino oseltamivir carboxylate () based on guanidine cyclic diimide (GCDI) to treat influenza viruses. By concealing the guanidine group, which significantly limits the intestinal absorption, its prodrugs s demonstrate dramatic improvement of oral bioavailability. The most promising antiviral substance readily forms covalent adducts with serum proteins via a degradable linker after the intestinal absorption.
View Article and Find Full Text PDFMol Pharm
September 2024
Centre for Applied Pharmacokinetic Research, School of Health Sciences, University of Manchester, Manchester M13 9PL, U.K.
Modulation of the transport-mediated active uptake by human serum albumin (HSA) for highly protein-bound substrates has been reported and improved the -to- extrapolation (IVIVE) of hepatic clearance. However, evidence for the relevance of such a phenomenon in the case of renal transporters is sparse. In this study, transport of renal organic anion transporter 1 or 3 (OAT1/3) substrates into conditionally immortalized proximal tubular epithelial cells transduced with OAT1/3 was measured in the presence and absence of 1 and 4% HSA while keeping the unbound substrate concentration constant (based on measured fraction unbound, ).
View Article and Find Full Text PDFEur J Med Chem
November 2024
School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, PR China. Electronic address:
Neuraminidase (NA) has been well-studied as a therapeutic target for Influenza. However, resistance to the influenza virus has been observed recently. Out of special interest in the utilization of dietary antivirals from citrus, in vitro inhibition activity against NA and in silico studies including molecular docking, molecular dynamic simulation, and a predictive ADMET study, were performed on five citrus-derived flavanones.
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