Individualized treatment based on CYP3A5 single-nucleotide polymorphisms with tacrolimus in ulcerative colitis.
CYP3A5
Colitis, ulcerative
Individualized treatment
Tacrolimus
Journal
Intestinal research
ISSN: 1598-9100
Titre abrégé: Intest Res
Pays: Korea (South)
ID NLM: 101572802
Informations de publication
Date de publication:
Apr 2019
Apr 2019
Historique:
received:
22
08
2018
accepted:
05
12
2018
pubmed:
2
2
2019
medline:
2
2
2019
entrez:
2
2
2019
Statut:
ppublish
Résumé
The pharmacokinetics of tacrolimus (TAC) is known to be largely influenced by single-nucleotide polymorphisms (SNPs) in CYP3A5. Patients starting TAC require careful dose adjustment, owing to the wide range of optimal dosages, depending on their CYP3A5 expression status. Here, we evaluated whether individualization of TAC dosages based on CYP3A5 SNPs would improve its therapeutic efficacy in ulcerative colitis. Twenty-one patients were prospectively treated, with their initial dosage adjusted according to their CYP3A5 status (0.1, 0.15, and 0.2 mg/kg/day for CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1, respectively). Their clinical outcomes were compared with those of patients treated with a fixed dose (0.1 mg/kg/day). The first blood trough level of CYP3A5 expressors, CYP3A5*1/*3 or CYP3A5*1/*1, and the overall rate in achieving the target blood trough level within a week in the individualized-dose group were significantly higher than those in the fixed-dose group (5.15±2.33 ng/mL vs. 9.63±0.79 ng/mL, P=0.035 and 12.5% vs. 66.7%, P=0.01). The remission rate at 2 weeks in the expressors was as high as that in the nonexpressors, CYP3A5*3/*3, in the individualized-dose group. Individualized TAC treatment is effective against ulcerative colitis regardless of the CYP3A5 genotype.
Sections du résumé
BACKGROUND/AIMS
OBJECTIVE
The pharmacokinetics of tacrolimus (TAC) is known to be largely influenced by single-nucleotide polymorphisms (SNPs) in CYP3A5. Patients starting TAC require careful dose adjustment, owing to the wide range of optimal dosages, depending on their CYP3A5 expression status. Here, we evaluated whether individualization of TAC dosages based on CYP3A5 SNPs would improve its therapeutic efficacy in ulcerative colitis.
METHODS
METHODS
Twenty-one patients were prospectively treated, with their initial dosage adjusted according to their CYP3A5 status (0.1, 0.15, and 0.2 mg/kg/day for CYP3A5*3/*3, CYP3A5*1/*3, and CYP3A5*1/*1, respectively). Their clinical outcomes were compared with those of patients treated with a fixed dose (0.1 mg/kg/day).
RESULTS
RESULTS
The first blood trough level of CYP3A5 expressors, CYP3A5*1/*3 or CYP3A5*1/*1, and the overall rate in achieving the target blood trough level within a week in the individualized-dose group were significantly higher than those in the fixed-dose group (5.15±2.33 ng/mL vs. 9.63±0.79 ng/mL, P=0.035 and 12.5% vs. 66.7%, P=0.01). The remission rate at 2 weeks in the expressors was as high as that in the nonexpressors, CYP3A5*3/*3, in the individualized-dose group.
CONCLUSIONS
CONCLUSIONS
Individualized TAC treatment is effective against ulcerative colitis regardless of the CYP3A5 genotype.
Identifiants
pubmed: 30704156
pii: ir.2018.00117
doi: 10.5217/ir.2018.00117
pmc: PMC6505090
doi:
Types de publication
Journal Article
Langues
eng
Pagination
218-226Références
Clin Pharmacol Ther. 1999 Sep;66(3):288-94
pubmed: 10511065
Clin Pharmacol Ther. 2000 Jan;67(1):48-56
pubmed: 10668853
J Clin Pharmacol. 2001 Mar;41(3):289-97
pubmed: 11269569
Nat Genet. 2001 Apr;27(4):383-91
pubmed: 11279519
Annu Rev Pharmacol Toxicol. 2003;43:285-307
pubmed: 12359865
Immunol Today. 1992 Apr;13(4):136-42
pubmed: 1374612
Anal Biochem. 2004 Apr 15;327(2):215-21
pubmed: 15051538
Transplantation. 2004 Oct 27;78(8):1182-7
pubmed: 15502717
Transplant Proc. 2005 May;37(4):1730-2
pubmed: 15919447
Gut. 2006 Sep;55(9):1255-62
pubmed: 16484504
Pharmacol Ther. 2006 Oct;112(1):184-98
pubmed: 16759707
Clin Gastroenterol Hepatol. 2007 Jan;5(1):103-10
pubmed: 17142106
Lancet. 2007 May 12;369(9573):1627-40
pubmed: 17499605
Br J Clin Pharmacol. 2008 Jul;66(1):154-5
pubmed: 18341670
Eur J Clin Pharmacol. 2009 May;65(5):473-81
pubmed: 19125240
Clin J Am Soc Nephrol. 2009 Feb;4(2):481-508
pubmed: 19218475
J Crohns Colitis. 2010 Oct;4(4):431-7
pubmed: 21122540
Clin Pharmacol Ther. 2011 Mar;89(3):422-8
pubmed: 21289623
Inflamm Bowel Dis. 2012 May;18(5):803-8
pubmed: 21887732
Int J Mol Med. 2011 Dec;28(6):1093-102
pubmed: 21922127
Pharmacogenet Genomics. 2013 Oct;23(10):563-85
pubmed: 23922006
J Gastroenterol Hepatol. 2014 Jan;29(1):60-6
pubmed: 24033383
J Crohns Colitis. 2016 Apr;10(4):484-94
pubmed: 26645641
J Gastroenterol Hepatol. 2017 Sep;32(9):1562-1569
pubmed: 28135009
J Crohns Colitis. 2017 Jul 1;11(7):769-784
pubmed: 28513805
J Gastroenterol. 2018 Mar;53(3):305-353
pubmed: 29429045
Am J Health Syst Pharm. 1995 Jul 15;52(14):1521-35
pubmed: 7552894