The influence of labour on the pharmacokinetics of intravenously administered amoxicillin in pregnant women.
OBJECTIVE
Many physiological changes take place during pregnancy and labour. These might change the pharmacokinetics of amoxicillin, necessitating adjustment of the dose for prevention of neonatal infections. We investigated the influence of labour on the pharmacokinetics of amoxicillin.


METHODS
Pregnant women before and during labour were recruited and treated with amoxicillin intravenously. A postpartum dose was offered. Blood samples were obtained and amoxicillin concentrations were determined using high-pressure liquid chromatography. The pharmacokinetics were characterized by nonlinear mixed-effects modelling using NONMEM.


RESULTS
The pharmacokinetics of amoxicillin in 34 patients was best described by a three-compartment model. Moderate interindividual variability was identified in CL, central and peripheral volumes of distribution. The volume of distribution (V) increased with an increasing amount of oedema. Labour influenced the parameter estimate of peripheral volume of distribution (V(2)). V(2) was decreased during labour, and even more in the immediate postpartum period. For all patients the population estimates (mean +/- SE) for CL and V were 21.1 +/- 4.1 l h(-1) (CL), 8.7 +/- 6.6 l (V(1)), 11.8 +/- 7.7 l (V(2)) and 20.5 +/- 15.4 l (V(3)) respectively.


CONCLUSIONS
The peripheral distribution volume of amoxicillin in pregnant women during labour and immediately postpartum is decreased. However, these changes are not clinically relevant and do not warrant deviations from the recommended dosing regimen for amoxicillin during labour in healthy pregnant patients.
Muller
Anouk E
AE
Erasmus MC, University Medical Centre Rotterdam, Department of Medical Microbiology and Infectious Diseases, Rotterdam, The Netherlands. muller.research@gmail.com
Dörr
P Joep
PJ
Mouton
Johan W
JW
De Jongh
Joost
J
Oostvogel
Paul M
PM
Steegers
Eric A P
EA
Voskuyl
Rob A
RA
Danhof
Meindert
M
D000328:Adult; D000658:Amoxicillin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000188:drug therapy; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D007743:Labor, Obstetric / Q000378:metabolism*; D008657:Metabolic Clearance Rate; D011247:Pregnancy; D011256:Pregnancy Outcome
D000900:Anti-Bacterial Agents; D000658:Amoxicillin