The influence of uterine contractions during labour on the pharmacokinetics of intravenously administered amoxicillin
Abstract number: 1733_868
Muller A.E., Dörr P.J., Mouton J.W., DeJongh J., Oostvogel P.M., Steegers E.A.P., Voskuyl R.A., Danhof M.
Objectives: Amoxicillin is widely used in pregnant women, both in those who are in labour and those who are not. An effect of labour on the pharmacokinetics of ampicillin has been shown previously, but similar data are not available for amoxicillin. Changes in the pharmacokinetics due to uterine contractions may pose these patients at risk for inappropriate dosing. We investigated the effects of uterine contractions on the pharmacokinetics of amoxicillin.
Methods: Healthy women at 3042 weeks of gestation were eligible for the study. They received amoxicillin following the local guidelines. From each patient 528 serial blood samples were taken and demographic data recorded. Serum antibiotic concentrations were determined by a validated HPLC method. Pharmacokinetic parameters and the influence of uterine contractions on these parameters were estimated by population pharmacokinetic modelling using NONMEM. Various models were tested. To discriminate between models the minimum value of the objective function (MVOF) was used.
Results: Thirty women were included, 20 without uterine contractions and 10 who were in labour. A three-compartment pharmacokinetic model best described the time course of amoxicillin. The estimated values (mean ±SE) for the entire population for clearance, volume of distribution of the peripheral compartments (V2 and V3) and the intercompartmental clearances (Q1 and Q2) were 21.6±0.99 L/h, 6.63±0.53, 8.65±0.99L, 35.8±5.15 and 5.95±0.65 L/h, respectively. The terminal half-life was 1.16±0.26 h. There was no effect of uterine contractions on the parameters, except on the volume of distribution of the central compartment (Vc). Uterine contractions slightly increased Vc from 6.93±1.73L to 8.64±2.21L (p < 0.05; mean ±SD). The residual error was found to be proportional to the blood concentrations. Interindividual variability was mainly due to differences in clearance and Vc. The main demographic characteristics did not influence the individual posthoc estimates for clearance.
Conclusion: A 3-compartment model best described the data. The consequential slow elimination is beneficial for the efficacy of amoxicillin, especially when it is used to prevent Streptococcus agalactiae infections in the neonate, because of the relatively low MICs. Both the absence of effects of uterine contractions and the lack of influence of patient characteristics indicate that dose-adjustments in this critical situation are not necessary.
|Session name:||European Society of Clinical Microbiology and Infectious Diseases|
|Location:||ICC, Munich, Germany|
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