Pharmacokinetic properties of azithromycin in pregnancy.
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.
School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
Sam
S
Salman
Stephen J
SJ
Rogerson
Kay
K
Kose
Susan
S
Griffin
Servina
S
Gomorai
Francesca
F
Baiwog
Josephine
J
Winmai
Josin
J
Kandai
Harin A
HA
Karunajeewa
Sean J
SJ
O'Halloran
Peter
P
Siba
Kenneth F
KF
Ilett
Ivo
I
Mueller
Timothy M E
TM
Davis
D000328:Adult; D000962:Antimalarials / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D017963:Azithromycin / Q000009:adverse effects / Q000493:pharmacokinetics*; D002738:Chloroquine / Q000009:adverse effects / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004338:Drug Combinations; D005260:Female; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D015233:Models, Statistical; D010219:Papua New Guinea; D011247:Pregnancy / Q000378:metabolism*; D011739:Pyrimethamine / Q000009:adverse effects / Q000493:pharmacokinetics; D013413:Sulfadoxine / Q000009:adverse effects / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry; D055815:Young Adult
D000962:Antimalarials; D004338:Drug Combinations; D017963:Azithromycin; D013413:Sulfadoxine; D002738:Chloroquine; D011739:Pyrimethamine