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Assessment of thiop...
Assessment of thiopurine methyltransferase and metabolite formation during thiopurine therapy : Results from a large swedish patient population
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- Hindorf, U. (författare)
- Division of Gastroenterology, Department of Internal Medicine, University Hospital, Lund, Sweden, Division of Gastroenterology, Department of Internal Medicine, University Hospital, SE-221 85 Lund, Sweden
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- Peterson, Curt (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Hälsouniversitetet,Klinisk farmakologi,Onkologiska kliniken US
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- Almer, Sven (författare)
- Östergötlands Läns Landsting,Linköpings universitet,Hälsouniversitetet,Gastroenterologi och hepatologi,Endokrin- och magtarmmedicinska kliniken US
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(creator_code:org_t)
- Ovid Technologies (Wolters Kluwer Health), 2004
- 2004
- Engelska.
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Ingår i: Therapeutic Drug Monitoring. - : Ovid Technologies (Wolters Kluwer Health). - 0163-4356 .- 1536-3694. ; 26:6, s. 673-678
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- This study examined thiopurine methyltransferase (TPMT) and the relationship to thioguanine nucleotides (TGN) and methylthioinosine monophosphate (meTIMP) in a large Swedish patient population. The current hypothesis is that the cytotoxic effects of thiopurine drugs are mediated by the incorporation of TGN into DNA. The authors assayed the TPMT activity in red blood cells from 1151 subjects and the concentrations of TGN (n = 602) and meTIMP (n = 593) from patients treated with thiopurine drugs. The TPMT frequency distribution in both adults and children showed some differences from what had been found in unselected general populations. Children had lower median TPMT activity than adults (12.0 versus 12.9 U/mL RBC, P < 0.001). Relative differences in both TGN formation [medians: normal TPMT, 1.3, intermediate TPMT, 3.3, low TPMT, 47.9 pmol/8 × 108 RBC per mg azathioprine (AZA), P < 0.001] and meTIMP formation (medians: normal TPMT, 13, intermediate TPMT, 7.3, low TPMT, 0 pmol/8 × 108 RBC per mg AZA, P = 0.001) per 1 mg administered drug were noted among the 3 TPMT activity groups. Women formed higher concentrations of both TGN (1.5 versus 1.3 pmol/8 × 108 RBC per mg AZA, P = 0.01) and meTIMP (14.4 versus 10.7 pmol/8 × 108 RBC per mg AZA, P = 0.01) than men did. There was a significant correlation between the AZA dose and the meTIMP concentrations (r = 0.45, P < 0.001). Furthermore, dose alterations made in subjects with normal TPMT (n = 84) and intermediate TPMT (n = 22) activity resulted in more pronounced increases in TGN concentrations (170 versus 30 pmol/8 × 10 8 RBC, P < 0.001) in intermediate TPMT activity, whereas in normal TPMT activity changes in meTIMP concentrations were more pronounced (1.3 versus 0 nmol/8 × 108 RBC, P < 0.001). In normal TPMT activity both metabolites increased in a dose-dependent fashion, whereas in intermediate TPMT activity only TGN concentrations increased. The results of this study demonstrate the dynamic nature of thiopurine metabolism and its importance for thiopurine dosing.
Nyckelord
- Drug monitoring
- Methylthioinosine monophosphate (meTIMP)
- Thioguanine nucleotides (TGN)
- Thiopurine drugs
- Thiopurine methyltransferase (TPMT)
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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