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Pharmacokinetics of...
Pharmacokinetics of 2-mercaptopropionylglycine (Tiopronin) in man
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- Carlsson, Margaretha S. (författare)
- Linköpings universitet,Klinisk kemi,Hematologi,Njurmedicin,Hälsouniversitetet
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- Sjöström, Per, Doktor (opponent)
- Medicinska Kliniken, Regionsjukhuset, Örebro
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(creator_code:org_t)
- ISBN 9178709261
- Linköping : Linköpings universitet, 1993
- Engelska 56 s.
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Serie: Linköping University Medical Dissertations, 0345-0082 ; 385
- Relaterad länk:
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https://urn.kb.se/re...
Abstract
Ämnesord
Stäng
- 2-Mercaptopropionylglycine (2-MPG, tiopronin) has been used successfully in the treatment of cystinuria despite the lack of knowledge of its pharmacokinetics. Therefore methods based on high-performance liquid chromatography and fluorometric detection were developed for quantitative analysis. The total, non-protein-bound, and free (thiolic) tiopronin were measured in plasma using this method.The phannacokinetic disposition of tiopronin in plasma after intravenous administration was best described by a three exponential function. Plasma concentration time-curves of total tiopronin exhibited a rapid distribution phase, a B-phase corresponding to renal excretion, and a long terminal elimination phase. The latter was the result of strong disulphide binding of tiopronin to proteins. The non-protein-bound tiopronin was eliminated faster judging by its early appearance in urine. Mean bioavailability was 63 % in healthy volunteers with great interindividual variability (range 33-91%).Multiple dosing studies gave similar pharrnacokinetic parameters as for single dose studies and studies on patients with renal impaitment elucidated the renal clearance of the drug. In vitro studies showed a slow dissolution of the drug dosage form employed. A metabolite, 2-mercaptopropionic acid, was identified and its pharmacokinetics was investigated. The mechanism of action of the drug is discussed based on the results of measuring free tiopronin in plasma.
Nyckelord
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- MEDICIN
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