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Pharmacokinetics of 2-mercaptopropionylglycine (Tiopronin) in man
Linköpings universitet, Institutionen för biomedicin och kirurgi, Klinisk kemi. Linköpings universitet, Institutionen för biomedicin och kirurgi, Hematologi. Linköpings universitet, Institutionen för medicin och vård, Njurmedicin. Linköpings universitet, Hälsouniversitetet.
1993 (engelsk)Doktoravhandling, med artikler (Annet vitenskapelig)
Abstract [en]

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.

sted, utgiver, år, opplag, sider
Linköping: Linköpings universitet , 1993. , s. 56
Serie
Linköping University Medical Dissertations, ISSN 0345-0082 ; 385
HSV kategori
Identifikatorer
URN: urn:nbn:se:liu:diva-25633Lokal ID: 10006ISBN: 91-7870-926-1 (tryckt)OAI: oai:DiVA.org:liu-25633DiVA, id: diva2:246181
Disputas
1993-04-30, Berzeliussalen, Universitetssjukhuset, Linköping, 09:00 (svensk)
Opponent
Merknad
Papers, included in the Ph.D. thesis, are not registered and included in the posts from 1999 and backwards.Tilgjengelig fra: 2009-10-08 Laget: 2009-10-08 Sist oppdatert: 2012-07-20bibliografisk kontrollert

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