%0 Journal Article
%T Bench to Bed Evidences for Pharmacokinetic and Pharmacodynamic Interactions Involving Oseltamivir and Chinese Medicine
%A Qi Chang
%A Siukwan Wo
%A Karry L. K. Ngai
%A Xiaoan Wang
%A Benny Fok
%A Teresa M. Ngan
%A Vivian T. Wong
%A Thomas Y. K. Chan
%A Vincent H. L. Lee
%A Brian Tomlinson
%A Paul K. S. Chan
%A Moses S. S. Chow
%A Zhong Zuo
%J Evidence-Based Complementary and Alternative Medicine
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/354172
%X Oseltamivir (OA), an ethyl ester prodrug of oseltamivir carboxylate (OC), is clinically used as a potent and selective inhibitor of neuraminidase. Chinese medicines have been advocated to combine with conventional drug for avian influenza. The current study aims to investigate the potential pharmacokinetic and pharmacodynamic interactions of a Chinese medicine formula, namely, Yin Qiao San and Sang Ju Yin (CMF1), commonly used for anti-influenza in combination with OA in both rat and human, and to reveal the underlined mechanisms. It was found that although , AUC and urinary recovery of OC, as well as metabolic ratio ( ), were significantly decreased in a dose-dependent manner following combination use of CMF1 and OA in rat studies ( ), such coadministration in 14 healthy volunteers only resulted in a trend of minor decrease in the related parameters. Further mechanistic studies found that although CMF1 could reduce absorption and metabolism of OA, it appears to enhance viral inhibition of OA ( ). In summary, although there was potential interaction between OA and CMF1 found in rat studies, its clinical impact was expected to be minimal. The coadministration of OA and CMF1 at the clinical recommended dosages is, therefore, considered to be safe. 1. Introduction Oseltamivir (OA) is clinically used as a potent and selective inhibitor of neuraminidase essential for replication of influenza A and B viruses. The normal adult dose of OA for the treatment of avian influenza is 75£¿mg orally twice a day for 5 days. Following 50£¿mg doses, the maximum plasma oseltamivir carboxylate concentration is about 230£¿¦Ìg/L, which is above of 50% inhibitory concentrations (IC50) of many influenza A viruses [1]. The pharmacokinetics of both OA and its active metabolite oseltamivir carboxylate (OC) have been studied in young healthy adults and children, as well as elderly subjects [1¨C4]. Following oral administration, OA is rapidly absorbed and extensively converted to OC, primarily by hepatic carboxylesterase enzymes, resulting in a much higher concentration in vivo than OA. The absolute oral bioavailability of OC from orally administered OA is 80% with a half-life of 6¨C10 hours and food has no significant effect on its bioavailability [1, 5]. The potential advantage of OA in combination with Chinese medicine (CM) is of interest since avian influenza can be deadly and it is an important health care goal in many Asian countries. In Hong Kong, the Hospital Authority Central Committee on Infectious Disease and Infection Control Branch Centre for Health Protection has jointly
%U http://www.hindawi.com/journals/ecam/2014/354172/