AAC Accepts, published online ahead of print on 26 October 2009

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Antimicrob. Agents Chemother. doi:10.1128/AAC.00771-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The pharmacokinetic properties of azithromycin in pregnancy

Sam Salman, Stephen J Rogerson, Kay Kose, Susan Griffin, Servina Gomorai, Francesca Baiwog, Josephine Winmai, Josin Kandai, Harin A Karunajeewa, Sean J O'Halloran, Peter Siba, Kenneth F Ilett, Ivo Mueller, and Timothy M E Davis^*

School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia; Faculty of Medicine, University of Melbourne, Melbourne, Australia; Papua New Guinea Institute of Medical Research, Madang, Papua New Guinea; Western Health, Melbourne, Australia; Clinical Pharmacology and Toxicology Laboratory, Path West Laboratory Medicine, Nedlands, Australia

^* To whom correspondence should be addressed. Email: tdavis{at}cyllene.uwa.edu.au.

Azithromycin (AZI) is an azalide antibiotic with antimalarial activity that is considered safe in pregnancy. To assess its pharmacokinetic properties when administered as intermittent preventive treatment in pregnancy (IPTp), two 2 g doses were given 24 h apart to 31 pregnant and 29 age-matched non-pregnant Papua New Guinean women. All subjects also received single-dose sulfadoxine-pyrimethamine (SP; 1500mg/75mg) or chloroquine (450 mg base daily for three days). Blood samples were taken at 0, 1, 2, 3, 6, 12, 24, 32, 40, 48 and 72 h, and on days 4, 5, 7, 10 and 14 for AZI assay by ultra high-performance liquid chromatography-tandem mass spectrometry. The treatments were well tolerated. Using population pharmacokinetic modelling, a three-compartment model with a zero- followed by first-order absorption and no lag time provided the best fit. The area under the plasma concentration-time curve (AUC_0–; 28.7 and 31.8 mg h L^-1 for pregnant and non-pregnant subjects, respectively) was consistent with results of previous studies, but the estimated terminal elimination half-lives (78 and 77 h, respectively) were generally longer. The only significant relationship for a range of potential covariates including malarial parasitemia was with pregnancy which accounted for an 86% increase in the volume of distribution of the central compartment relative to bioavailability without a significant change in AUC_0-. These data suggest that AZI can be combined with longer half-life compounds such as SP in combination IPTp without the need for dose adjustment.