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Ritrodrine: analysis, comparative maternal and fetal pharmacokinetics and pharmacodynamics in sheep

University of British Columbia

Ritodrine is a β-adrenoreceptor agonist that is used clinically in Europe, Australia and the United States as a tocolytic. Despite the relatively widespread pharmacological investigation of ritodrine in both human and animal species there is very little pharmacokinetic data. In fact, there are no estimates of any fetal pharmacokinetic parameter in any species. This thesis reports: 1) the development of a capillary gas chromatographic assay method using electron capture detection for the quantitation of ritodrine from the various biological fluids of the chronically instrumented pregnant sheep, ii) the placental and fetal non-placental clearances of ritodrine during constant rate fetal intravenous ritodrine infusion, iii) the disposition of ritodrine in some of the fluid compartments of the fetal lamb during and after constant rate fetal intravenous ritodrine infusion, iv) the maternal and fetal pharniacokinetics of ritodrine following maternal intravenous administration, v) the maternal and fetal pharmacological responses to ritodrine following maternal intravenous administration, vi) the fetal pharmacokinetics of ritodrine following fetal intravenous bolus administration, vii) the fetal pharmacological responses to ritodrine following fetal intravenous bolus administration, viii) the effects of a fetal intravenous ritodrine bolus administration on the regional blood flow distribution of the anaesthetised fetal lamb, ix) the comparative maternal and fetal pharmacokinetics of ritodrine in the sheep, x) the comparative pharmacological responsiveness of the ewe and fetus to ritodrine. In the course of this work a gas-chromatographic assay method using electron capture detection was developed for the quantitation of ritodrine. The developed method was sufficiently sensitive and selective to allow the determination of ritodrine from a variety of biological fluids from the chronically instrumented pregnant sheep. The minimum quantifiable concentration of ritodrine was 2.5 ng/mL from a 500 uL fluid sample. This method was used to quantitate ritodrine from all the fluid samples obtained during the pharmacokinetic studies. The developed assay method has been applied to the study of the clearance and disposition of ritodrine in the fetal lamb during and after constant rate fetal intravenous infusion. [more abstract]

Thesis/Dissertation

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2008-12-17

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http://hdl.handle.net/2429/3005

Pharmaceutical Sciences

University of British Columbia

UBCV

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