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25: Betamethasone in pregnancy: pharmacokinetics study to evaluate the correlation with maternal weight and multiple pregnancies

      Objective

      To 1) examine the pharmacokinetic (PK) parameters of standard dose betamethasone, between 24 and 34 weeks 2) determine whether Body Mass Index (BMI) or other body size indicators influence betamethasone volume of distribution and/or clearance 3) determine whether multiple gestations affect the PK parameters.

      Study Design

      Prospective population PK study. Five sampling times were identified to estimate PK parameters. Body size indicators were: actual body weight, BMI, lean body weight (LBW), and body surface area. Betamethasone plasma concentrations were measured using a liquid chromatography mass spectrometry assay and analyzed with nonlinear mixed effect modeling software, NONMEM. Both one and two compartment models with first order absorption and elimination were evaluated. Relationships between PK estimates and subject characteristics were analyzed by graphical and generalized additive model methods using S-Plus7 statistical software. Validity of the final population PK model was evaluated by bootstrap analysis. Power analysis showed 80% power to detect a 30% difference in clearance between women carrying twin gestations versus singleton.

      Results

      PK dataset included 292 blood samples from 78 patients, 66 singleton pregnancies and 12 multiple gestations. Two compartment model was superior in describing the disposition of betamethasone. Effects of different maternal body size indicators on PK parameters were measured; all four body size indicators significantly explained the inter-subject variability; however, greatest effect was seen for LBW. The relations between PK parameters and LBW remained linear throughout the range of maternal weights; this was not true for BMI. Multiple order of pregnancy did not affect any of the PK parameters studied.

      Conclusion

      We demonstrated that across a wide range of maternal body size, individualization of betamethasone dosage would be preferable in order to limit the risk of overdosing slim mothers and underdosing mothers with larger body size. We could not demonstrate any differences in singletons compared to multiples.