Pharmacokinetics of oseltamivir: an oral antiviral for the treatment and prophylaxis of influenza in diverse populations

被引:147
作者
Davies, Brian E. [1 ]
机构
[1] Hoffmann La Roche Inc, Nutley, NJ 07110 USA
关键词
mechanism of action; dosing; drug interactions; NEURAMINIDASE INHIBITOR; PRODRUG OSELTAMIVIR; DRUG; H5N1; TOLERABILITY; CARBOXYLATE; RWJ-270201; ZANAMIVIR; VIRUSES; GS4104;
D O I
10.1093/jac/dkq015
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Influenza is a transmissible viral pathogen that continues to cause substantial morbidity and mortality. Oseltamivir is an orally administered antiviral medication that selectively inhibits the influenza neuraminidase enzymes that are essential for viral replication. Treatment of infected children >= 1 year and adults of all ages may decrease the severity and duration of the symptoms of infection, while prophylactic dosing can prevent their onset. Oseltamivir is ingested in the form of a prodrug (oseltamivir phosphate) that is rapidly converted by hepatic esterases into the active metabolite, oseltamivir carboxylate. Oseltamivir carboxylate has high bioavailability and penetrates sites of infection at concentrations that are sufficient to inhibit viral replication. The pharmacokinetics of oseltamivir and oseltamivir carboxylate are dose proportional after repeated doses of up to 500 mg twice daily. This predictable profile means that oseltamivir is suitable for use in diverse patient populations, which may include young children and elderly patients, various ethnic groups and those with renal or hepatic impairment. As the potential for drug interactions is low, oseltamivir is also suitable for use in patients with co-morbid conditions who are likely to be receiving concomitant medications.
引用
收藏
页码:II5 / II10
页数:6
相关论文
共 26 条
[1]  
Aoki F., 2005, ANN M INF DIS SOC AM
[2]   Comparison of the anti-influenza virus activity of RWJ-270201 with those of oseltamivir and zanamivir [J].
Bantia, S ;
Parker, CD ;
Ananth, SL ;
Horn, LL ;
Andries, K ;
Chand, P ;
Kotian, PL ;
Dehghani, A ;
El-Kattan, Y ;
Lin, T ;
Hutchison, TL ;
Montgomery, JA ;
Kellog, DL ;
Babu, YS .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (04) :1162-1167
[3]   Wartime tactic doubles power of scarce bird-flu drug [J].
Butler, D .
NATURE, 2005, 438 (7064) :6-6
[4]  
DAVIES BE, 2009, 49 INT C ANT AG CHEM
[5]   Penetration of GS4071, a novel influenza neuraminidase inhibitor, into rat bronchoalveolar lining fluid following oral administration of the prodrug GS4104 [J].
Eisenberg, EJ ;
Bidgood, A ;
Cundy, KC .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1997, 41 (09) :1949-1952
[6]  
GIESCHKE R, 2007, OPT CONTR INFL 6 C T
[7]   Comparison of efficacies of RWJ-270201, zanamivir, and oseltamivir against H5N1, H9N2, and other avian influenza viruses [J].
Govorkova, EA ;
Leneva, IA ;
Goloubeva, OG ;
Bush, K ;
Webster, RG .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2001, 45 (10) :2723-2732
[8]   Clinical pharmacokinetics of the prodrug oseltamivir and its active metabolite Ro 64-0802 [J].
He, G ;
Massarella, J ;
Ward, P .
CLINICAL PHARMACOKINETICS, 1999, 37 (06) :471-484
[9]   The anti-influenza drug oseltamivir exhibits low potential to induce pharmacokinetic drug interactions via renal secretion - Correlation of in vivo and in vitro studies [J].
Hill, G ;
Cihlar, T ;
Oo, C ;
Ho, ES ;
Prior, K ;
Wiltshire, H ;
Barrett, J ;
Liu, BL ;
Ward, P .
DRUG METABOLISM AND DISPOSITION, 2002, 30 (01) :13-19
[10]   Pharmacokinetics and tolerability of oseltamivir combined with probenecid [J].
Holodniy, Mark ;
Penzak, Scott R. ;
Straight, Timothy M. ;
Davey, Richard T. ;
Lee, Kelvin K. ;
Goetz, Matthew Bidwell ;
Raisch, Dennis W. ;
Cunningham, Francesca ;
Lin, Emil T. ;
Olivo, Noemi ;
Deyton, Lawrence R. .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2008, 52 (09) :3013-3021