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

Abstract

AIMSMany 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. METHODSPregnant 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. RESULTSThe 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 Ϯ SE) for CL and V were 21.1 Ϯ 4.1 l h -1 (CL), 8.7 Ϯ 6.6 l (V1), 11.8 Ϯ 7.7 l (V2) and 20.5 Ϯ 15.4 l (V3) respectively. CONCLUSIONSThe 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.

Pregnancy‐related pharmacokinetic changes

“…In addition, if there is no change in clearance, an increase in volume of distribution will increase the half‐life of the drug, which potentially could impact the dosing interval. Intravenously administered amoxicillin volume of distribution beta was higher during pregnancy than postpartum . In addition, initial amoxicillin volume of distribution increased with increasing maternal edema .…”

“…54 In addition, initial amoxicillin volume of distribution increased with increasing maternal edema. 54 Other drugs (e.g., thiopental, theophylline, and immune globulin) have also been reported to have increased volumes of distribution during pregnancy. [55][56][57][58] Absorption Pregnancy is associated with multiple changes in gastrointestinal motility, such as delayed gastric emptying, slowed small intestinal motility, and delayed colonic emptying, which potentially could alter oral absorption, as depicted in Figure 1.…”

“…Intravenously administered amoxicillin volume of distribution beta was higher during pregnancy than postpartum . In addition, initial amoxicillin volume of distribution increased with increasing maternal edema . Other drugs (e.g., thiopental, theophylline, and immune globulin) have also been reported to have increased volumes of distribution during pregnancy …”

Inclusion of pregnant and breastfeeding women in research – efforts and initiatives

“…narcotics). Despite the regular use of these drugs during labour, the influence of labour on the PK of these drugs has been scarcely studied . PK studies during labour deal not only with ethical issues, but also with practical difficulties.…”

Money makes the world go round: the pervasiveness of pharmacoeconomics

“…We hoped that this would stimulate work in this important area and it is a pleasure to see an acceleration in submission rate of first rate papers across the spectrum of paediatric clinical pharmacology that has followed [see for example 11–15]. The current issue is particularly rich in papers addressing a wide range of topics of paediatric relevance spanning the influence of labour on the pharmacokinetics (PK) of amoxicillin [16], population PK of diclofenac for acute pain in children [17], a PK and pharmacogenetic analysis of 6‐mercaptopurine in children with acute lymphoblastic leukemia [18], the efficacy and safety of dexibuprofen compared with the racemate in children with respiratory infections [19], and the public awareness and opinions on the use of unlicensed medicines in children [20].…”