The influence of labour on the pharmacokinetics of intravenously administered amoxicillin in pregnant women

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Examples exist that pharmacokinetics of drugs in pregnant women can differ from that in non-pregnant individuals.
• In pregnant women before the onset of labour, the pharmacokinetics of amoxicillin is similar to that in non-pregnant individuals, but for women during labour this is unknown.

WHAT THIS STUDY ADDS

• Labour influences the pharmacokinetics of amoxicillin.
• During labour and even more in the immediate postpartum period, the peripheral volume of distribution was decreased compared with pregnant women before the onset of labour.
• The volume of distribution increases with an increasing amount of oedema.

AIMS

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 (V₂). V₂ 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 (V₁), 11.8 ± 7.7 l (V₂) and 20.5 ± 15.4 l (V₃) 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.