This Article Full Text Full Text (PDF) Other Versions of this Article: AAC.00852-06v1 51/1/103    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Liu, P. Articles by Sharma, A. Search for Related Content PubMed PubMed Citation Articles by Liu, P. Articles by Sharma, A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, January 2007, p. 103-109, Vol. 51, No. 1
0066-4804/07/$08.00+0     doi:10.1128/AAC.00852-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Comparative Pharmacokinetics of Azithromycin in Serum and White Blood Cells of Healthy Subjects Receiving a Single-Dose Extended-Release Regimen versus a 3-Day Immediate-Release Regimen

Department of Clinical Pharmacology,¹ Department of Infectious Diseases, Pfizer Global Research & Development, New London, Connecticut,² Sourland Biostatistics, Ringoes, New Jersey,³ PHAROS GmbH, Ulm, Germany⁴

Received 12 July 2006/ Returned for modification 20 August 2006/ Accepted 15 October 2006

The pharmacokinetic profiles of azithromycin given as a single-dose regimen (2.0-g extended-release microspheres) were characterized in serum and white blood cells (WBC) and compared with those of a 3-day regimen (a 500-mg immediate-release tablet once daily; total dose, 1.5 g) in an open-label, randomized, parallel-group study of 24 healthy adult subjects. Serial blood samples were collected up to 5 days after the start of dosing for both regimens. Safety assessments were conducted throughout the study. A single 2.0-g dose of azithromycin microspheres achieved significantly higher exposures in serum and WBC during the first 24 h after the start of dosing than a 3-day regimen: an approximately threefold higher area under the curve from time zero to 24 h postdose (AUC_0-24) and an approximately twofold higher mean peak concentration on day 1. The single-dose regimen provided total azithromycin exposures in serum and WBC similar to those of the 3-day regimen, as evidenced by the similar AUC_0-120 and trough azithromycin concentrations in serum and WBC (mononuclear leukocytes [MNL] and polymorphonuclear leukocytes [PMNL]). For both regimens, the average total azithromycin exposures in MNL and PMNL were approximately 300- and 600-fold higher than those in serum. Azithromycin concentrations in MNL and PMNL remained above 10 µg/ml for at least 5 days after the start of dosing for both regimens. This "front-loading" of the dose on day 1 is safely achieved by the extended-release microsphere formulation, which maximizes the drug exposure at the time when the bacterial burden is likely to be highest.

Published ahead of print on 23 October 2006.

This article has been cited by other articles:

• Lucchi, M., Damle, B., Fang, A., de Caprariis, P. J., Mussi, A., Sanchez, S. P., Pasqualetti, G., Del Tacca, M. (2008). Pharmacokinetics of azithromycin in serum, bronchial washings, alveolar macrophages and lung tissue following a single oral dose of extended or immediate release formulations of azithromycin. J Antimicrob Chemother 61: 884-891 [Abstract] [Full Text]