QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Résumé Extracto Full Text PDF Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Articles Ahead of Print [Order Reprint] Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Abe, M. Articles by Rayner, C. R Search for Related Content PubMed PubMed Citation Articles by Abe, M. Articles by Rayner, C. R

INFECTIOUS DISEASES

Pharmacokinetics of Oseltamivir in Young and Very Elderly Subjects

Clinical Pharmacologist, Department of Clinical Pharmacology, Chugai Clinical Research Center Co. Ltd, Tokyo, Japan

James Smith, PhD

International Medical Leader, F Hoffman-La Roche Ltd, Basel, Switzerland

Akinori Urae, MD PhD

Chief Executive, Mediscience Planning Inc, Tokyo

Joanne Barrett, PhD

Clinical Pharmacologist, Department of Medical Science, Roche Products Ltd, Welwyn Garden City, Herts, UK

Haruki Kinoshita, MSc

Department Manager, Department of Clinical Pharmacology, Chugai Clinical Research Center Co. Ltd, Tokyo

Craig R Rayner, PharmD

Clinical Pharmacologist, Department of Medical Science, Roche Products Ltd, Welwyn Garden City

Reprints: Mr. Abe, Department of Clinical Pharmacology, Chugai Clinical Research Center Co. Ltd, 2-1-1 Nihonbashi Muromachi Chuo-Ku, Tokyo, 103-8324 Japan, fax 81 3 3281 0819, abemsi{at}chugai-pharm.co.jp

BACKGROUND: Pharmacokinetic studies of oseltamivir in very elderly patients (80 y) have not previously been performed.

OBJECTIVE: To compare the pharmacokinetics of oseltamivir and the active carboxylate metabolite in healthy young and very elderly Japanese subjects.

METHODS: Young (20-35 y, fasting, n = 7) and very elderly subjects (80 y, fed, n = 5) were enrolled in single-center studies and received a single oral dose of oseltamivir 75 mg. Plasma and urine samples were collected (24 h) for pharmacokinetic analysis, and safety was assessed.

RESULTS: The time to maximum plasma concentration (t_max) for oseltamivir was delayed in the very elderly compared with the young subjects (2.30 vs 0.71 h, respectively). Furthermore, oseltamivir maximum plasma concentration (C_max) and AUC_inf were 52% and 80% higher, respectively, in the very elderly compared with the young subjects. Oral clearance was 45% lower in elderly patients, possibly due to the effects of administration of oseltamivir with a meal. For the active metabolite, oseltamivir carboxylate, C_max and AUC_inf values were, respectively, 22% and 91% higher in the very elderly subjects than in the young subjects, while oral clearance was 50% lower in the elderly population. The increased exposure of the active metabolite is likely to correlate with an age-related decline in renal function. For both oseltamivir and the active metabolite, there was large interpatient variability in the C_max values. The data reported here indicate that oseltamivir would be effective in both of these populations, as trough concentrations for the active metabolite at 12 and 24 hours exceeded the 50% inhibitory concentration against the neuraminidase of influenza A and B isolates by more than 50-fold. Oseltamivir was well tolerated in both groups.

CONCLUSIONS: Exposures (AUC_inf) to both the parent drug and active metabolite were increased by more than 80% in the small number of very elderly subjects presented here. However, oseltamivir was well tolerated by these subjects.

Key Words: geriatrics, oseltamivir, pharmacokinetics

Published Online, August 29, 2006. www.theannals.com, DOI 10.1345/aph.1H174

This article has been cited by other articles:

				Y. Wattanagoon, K. Stepniewska, N. Lindegardh, S. Pukrittayakamee, U. Silachamroon, W. Piyaphanee, T. Singtoroj, W. Hanpithakpong, G. Davies, J. Tarning, et al. Pharmacokinetics of High-Dose Oseltamivir in Healthy Volunteers Antimicrob. Agents Chemother., March 1, 2009; 53(3): 945 - 952. [Abstract] [Full Text] [PDF]

				S. W. Casscells, E. Granger, A. M. Kress, A. Linton, M. Madjid, and L. Cottrell Use of Oseltamivir After Influenza Infection Is Associated With Reduced Incidence of Recurrent Adverse Cardiovascular Outcomes Among Military Health System Beneficiaries With Prior Cardiovascular Diseases Circ Cardiovasc Qual Outcomes, March 1, 2009; 2(2): 108 - 115. [Abstract] [Full Text] [PDF]

				M. Holodniy, S. R. Penzak, T. M. Straight, R. T. Davey, K. K. Lee, M. B. Goetz, D. W. Raisch, F. Cunningham, E. T. Lin, N. Olivo, et al. Pharmacokinetics and Tolerability of Oseltamivir Combined with Probenecid Antimicrob. Agents Chemother., September 1, 2008; 52(9): 3013 - 3021. [Abstract] [Full Text] [PDF]

				D. Shi, J. Yang, D. Yang, E. L. LeCluyse, C. Black, L. You, F. Akhlaghi, and B. Yan Response to Comments on "Anti-Influenza Prodrug Oseltamivir Is Activated by Carboxylesterase Human Carboxylesterase 1, and the Activation Is Inhibited by Antiplatelet Agent Clopidogrel" J. Pharmacol. Exp. Ther., July 1, 2007; 322(1): 424 - 425. [Full Text] [PDF]

				J. J. Schentag, G. Hill, T. Chu, and C. R. Rayner Similarity in Pharmacokinetics of Oseltamivir and Oseltamivir Carboxylate in Japanese and Caucasian Subjects J. Clin. Pharmacol., June 1, 2007; 47(6): 689 - 696. [Abstract] [Full Text] [PDF]