Extended thiopurine metabolite assessment during 6-thioguanine therapy for immunomodulation in Crohn's disease.
J Clin Pharmacol
; 47(2): 187-91, 2007 Feb.
Article
em En
| MEDLINE
| ID: mdl-17244769
ABSTRACT
The proposed metabolic advantage of 6-thioguanine (6-TG) is the direct conversion into the pharmacologically active 6-thioguaninenucleotides (6-TGN). The authors assessed metabolic characteristics of 6-TG treatment in patients with Crohn's disease (N = 7) on therapy with 20 mg 6-TG. 6-thioguanine-monophosphate (6-TGMP), 6-thioguanine-diphosphate (6-TGDP), and 6-thioguanine-triphosphate (6-TGTP) were measured by high-performance liquid chromatography analysis in erythrocytes. Thiopurine S-methyltransferase activity and total 6-TGN levels were determined by standard methods. High interindividual variance in metabolite measurements was observed. Main metabolites were 6-TGTP (median = 531 pmol/8 x 10(8) red blood cells) and 6-TGDP (median = 199 pmol/8 x 10(8) red blood cells). Traces of 6-TGMP (median = 39 pmol/8 x 10(8) red blood cells) and 6-TG (2 patients) could be detected. 6-TGN levels correlated with 6-TGTP levels (r = 0.929, P = .003) and with the sum of separate nucleotides (r = 0.929, P = .003). No correlations were established between TPMT activity (median = 13 pmol/h/10(7)) and 6-TG metabolites. The 1-step metabolism of 6-TG still leads to high interindividual variance in metabolite concentrations. Total 6-TGN level monitoring may suffice for clinical practice.
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Base de dados:
MEDLINE
Assunto principal:
Tioguanina
/
Tionucleotídeos
/
Doença de Crohn
/
Nucleotídeos de Guanina
/
Imunossupressores
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Clin Pharmacol
Ano de publicação:
2007
Tipo de documento:
Article
País de afiliação:
Holanda