Effect of CYP3A5 and ABCB1 polymorphisms on the interaction between tacrolimus and itraconazole in patients with connective tissue disease.
Eur J Clin Pharmacol
; 71(9): 1091-7, 2015 Sep.
Article
en En
| MEDLINE
| ID: mdl-26184414
ABSTRACT
PURPOSE:
The aim of this study was to investigate the effect of itraconazole (ITCZ), a potent inhibitor of CYP3A4 and P-glycoprotein, on the blood concentration 12 h after tacrolimus administration (C 12h) in relation to CYP3A5 6986A>G and ABCB1 3435C>T genotype status in patients with connective tissue disease (CTD).METHODS:
Eighty-one CTD patients taking tacrolimus (Prograf®) once daily at night (2100 hours) were enrolled in this study. Whole blood samples were collected 12 h after tacrolimus administration at steady state.RESULTS:
The dose-adjusted tacrolimus C 12h with or without ITCZ co-administration was significantly higher in patients with CYP3A5*3/*3 than in those with the CYP3A5*1 allele [CYP3A5 *1/*1 vs. *1/*3 vs. *3/*3 = 1.67 vs. 2.70 vs. 4.83 ng/mL/mg (P = 0.003) and 0.68 vs. 0.97 vs. 2.20 ng/mL/mg (P < 0.001), respectively], but differences were not observed for ABCB1 genotypes. However, there was no difference in the increase rate of the dose-adjusted C 12h of tacrolimus between CYP3A5 or ABCB1 genotypes (P = 0.378 and 0.259). On the other hand, reduction of the estimated glomerular filtration rate exhibited a correlation with the C 12h of tacrolimus after ITCZ co-administration (r = -0.482, P = 0.009).CONCLUSIONS:
In CYP3A5*3/*3 patients, because the metabolic pathway for tacrolimus occurs only through CYP3A4, the combination with ITCZ seems to lead to a higher risk of acute renal dysfunction. Therefore, we suggest that the target blood tacrolimus concentration be set as low as possible through dose-adjustment for patients with the CYP3A5*3/*3 allele.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Tacrolimus
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Itraconazol
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Enfermedades del Tejido Conjuntivo
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Polimorfismo de Nucleótido Simple
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Citocromo P-450 CYP3A
/
Inmunosupresores
Límite:
Adolescent
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Adult
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Aged
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Female
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Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Eur J Clin Pharmacol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Japón