Pharmacokinetic properties of azithromycin in pregnancy.

Abstract:

: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 nonpregnant Papua New Guinean women. All subjects also received single-dose sulfadoxine-pyrimethamine (SP) (1,500 mg or 75 mg) or chloroquine (450-mg base daily for 3 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 modeling, a three-compartment model with zero-order followed by first-order absorption and no lag time provided the best fit. The areas under the plasma concentration-time curve (AUC(0-infinity)) (28.7 and 31.8 mg.h liter(-1) for pregnant and nonpregnant subjects, respectively) were consistent with the 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 the AUC(0-infinity). These data suggest that AZI can be combined with compounds with longer half-lives, such as SP, in combination IPTp without the need for dose adjustment.

authors

Salman S,Rogerson SJ,Kose K,Griffin S,Gomorai S,Baiwog F,Winmai J,Kandai J,Karunajeewa HA,O'Halloran SJ,Siba P,Ilett KF,Mueller I,Davis TM

doi

10.1128/AAC.00771-09

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

360-6

issue

1

eissn

0066-4804

issn

1098-6596

pii

AAC.00771-09

journal_volume

54

pub_type

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