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Long-term clinical impact of adaptation of initial tacrolimus dosing to CYP3A5 genotype
- Source :
- American Journal of Transplantation, American Journal of Transplantation, 2016, 16 (9), pp.2670-2675. ⟨10.1111/ajt.13788⟩, American Journal of Transplantation, Wiley, 2016, 16 (9), pp.2670-2675. ⟨10.1111/ajt.13788⟩, American Journal of Transplantation, Wiley, 2016, 16 (9), pp.2670-2675. 〈10.1111/ajt.13788〉
- Publication Year :
- 2016
- Publisher :
- HAL CCSD, 2016.
-
Abstract
- International audience; Pretransplantation adaptation of the daily dose of tacrolimus to CYP3A5 genotype is associated with improved achievement of target trough concentration (C0 ), but whether this improvement affects clinical outcomes is unknown. In the present study, we have evaluated the long-term clinical impact of the adaptation of initial tacrolimus dosing according to CYP3A5 genotype: the transplantation outcomes of the 236 kidney transplant recipients included in the Tactique study were retrospectively investigated over a period of more than 5 years. In the Tactique study, patients were randomly assigned to receive tacrolimus at either a fixed dosage or a dosage determined by their genotype, and the primary efficacy end point was the proportion of patients for whom tacrolimus C0 was within target range (10-15 ng/ml) at day 10. Our results indicate that the incidence of biopsy proven acute rejection and graft survival were similar between the control and the adapted tacrolimus dose groups, as well as between the patients who achieve the tacrolimus C0 target ranges earlier. Parients death, cancer, cardiovascular events and infections were also similar, and renal function did not change. We conclude that optimization of initial tacrolimus dose using pharmacogenetic testing does not improve clinical outcomes.
- Subjects :
- [ SDV.MHEP.UN ] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology
Graft Rejection
Male
immunosuppressant
[SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery
translational research/science
kidney transplantation/nephrology
immunosuppression/immune modulation
Pharmacology
Kidney Function Tests
030226 pharmacology & pharmacy
[SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology
0302 clinical medicine
Risk Factors
Cytochrome P-450 CYP3A
Immunology and Allergy
Medicine
Tissue Distribution
Pharmacology (medical)
genetics
Prospective Studies
[ SDV.MHEP.CHI ] Life Sciences [q-bio]/Human health and pathology/Surgery
Prospective cohort study
Kidney transplantation
Incidence (epidemiology)
Graft Survival
Middle Aged
Prognosis
3. Good health
surgical procedures, operative
030220 oncology & carcinogenesis
[SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Female
pharmacokinetics/pharmacodynamics
Immunosuppressive Agents
Glomerular Filtration Rate
medicine.medical_specialty
Genotype
Renal function
chemical and pharmacologic phenomena
[SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery
clinical research/practice
Tacrolimus
calcineurin inhibitor: tacrolimus
03 medical and health sciences
patient survival
Internal medicine
Humans
Dosing
CYP3A5
Transplantation
Dose-Response Relationship, Drug
business.industry
[ SDV.SP.PHARMA ] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
medicine.disease
Kidney Transplantation
[SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology
Pharmacogenetics
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Kidney Failure, Chronic
business
Follow-Up Studies
Subjects
Details
- Language :
- English
- ISSN :
- 16006135 and 16006143
- Database :
- OpenAIRE
- Journal :
- American Journal of Transplantation, American Journal of Transplantation, 2016, 16 (9), pp.2670-2675. ⟨10.1111/ajt.13788⟩, American Journal of Transplantation, Wiley, 2016, 16 (9), pp.2670-2675. ⟨10.1111/ajt.13788⟩, American Journal of Transplantation, Wiley, 2016, 16 (9), pp.2670-2675. 〈10.1111/ajt.13788〉
- Accession number :
- edsair.doi.dedup.....867b5c82bc695efae3fd5e781460154b