دورية أكاديمية
The effects of the CYP3A5*3 variant on tacrolimus pharmacokinetics and outcomes in Tunisian kidney transplant recipients.
| العنوان: | The effects of the CYP3A5*3 variant on tacrolimus pharmacokinetics and outcomes in Tunisian kidney transplant recipients. |
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| المؤلفون: | Charfi R; University of Tunis El Manar, Faculty of de Medicine of Tunis. National Centre Chalbi Belkahia of Pharmacovigilance, Department of clinical pharmacology, Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), 1006 Tunis, Tunisia., Bacha MM; Charles Nicolle hospital -Department of nephrology and internal medicine, Research Laboratory of Renal Pathology (LR00SP01), 1006 Tunis, Tunisie., Ben Fadhal M; Charles Nicolle hospital -Department of immunology, Research Laboratory of Immunology of Renal Transplantation and Immunopathology (LR03SP01), 1006 Tunis, Tunisia., Ferchichi K; University of Tunis El Manar, Faculty of de Medicine of Tunis. National Centre Chalbi Belkahia of Pharmacovigilance, Department of clinical pharmacology, Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), 1006 Tunis, Tunisia., El Jebari H; University of Tunis El Manar, Faculty of de Medicine of Tunis. National Centre Chalbi Belkahia of Pharmacovigilance, Department of clinical pharmacology, Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), 1006 Tunis, Tunisia., Gaies E; University of Tunis El Manar, Faculty of de Medicine of Tunis. National Centre Chalbi Belkahia of Pharmacovigilance, Department of clinical pharmacology, Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), 1006 Tunis, Tunisia., Klouz A; University of Tunis El Manar, Faculty of de Medicine of Tunis. National Centre Chalbi Belkahia of Pharmacovigilance, Department of clinical pharmacology, Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), 1006 Tunis, Tunisia., Abderrahim E; Charles Nicolle hospital -Department of nephrology and internal medicine, Research Laboratory of Renal Pathology (LR00SP01), 1006 Tunis, Tunisie., Ben Hamida F; Charles Nicolle hospital -Department of nephrology and internal medicine, Research Laboratory of Renal Pathology (LR00SP01), 1006 Tunis, Tunisie., Ben Abdallah T; Charles Nicolle hospital -Department of nephrology and internal medicine, Research Laboratory of Renal Pathology (LR00SP01), 1006 Tunis, Tunisie., Trabelsi S; University of Tunis El Manar, Faculty of de Medicine of Tunis. National Centre Chalbi Belkahia of Pharmacovigilance, Department of clinical pharmacology, Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), 1006 Tunis, Tunisia., Gorgi Y; Charles Nicolle hospital -Department of immunology, Research Laboratory of Immunology of Renal Transplantation and Immunopathology (LR03SP01), 1006 Tunis, Tunisia., Sfar I; Charles Nicolle hospital -Department of immunology, Research Laboratory of Immunology of Renal Transplantation and Immunopathology (LR03SP01), 1006 Tunis, Tunisia. |
| المصدر: | La Tunisie medicale [Tunis Med] 2023 Oct 05; Vol. 101 (10), pp. 738-744. Date of Electronic Publication: 2023 Oct 05. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Societe Tunisienne Des Sciences Medicales Country of Publication: Tunisia NLM ID: 0413766 Publication Model: Electronic Cited Medium: Internet ISSN: 2724-7031 (Electronic) Linking ISSN: 00414131 NLM ISO Abbreviation: Tunis Med Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Tunis : Societe Tunisienne Des Sciences Medicales |
| مواضيع طبية MeSH: | Tacrolimus*/therapeutic use , Kidney Transplantation*, Humans ; Immunosuppressive Agents/therapeutic use ; Cytochrome P-450 CYP3A/genetics ; Polymorphism, Single Nucleotide ; Genotype |
| مستخلص: | Introduction: Tacrolimus, exhibits interindividual pharmacokinetic variability and a narrow therapeutic index. The influence of the CYP3A5 6986A>G single nucleotide polymorphism (SNP) on this variability remains a topic of debate. Aim: To assess the impact of the aforementioned SNP on tacrolimus area under curve (AUC0-12h), adverse drug reactions (ADRs), and kidney graft outcomes. Methods: Blood samples were collected from Tunisian kidney transplants over a five-year period during either the early (<3 months) or late (>3 months) post-transplant phases. Through blood concentration (C0) and AUC0-12h of tacrolimus were measured. Patients were prospectively followed to assess graft outcomes. Polymerase chain reaction of restriction fragment length polymorphism was used for CYP3A5 6986A>G genotyping. Results: Fifty Tunisian kidney recipients receiving tacrolimus were enrolled in the study. Acute and chronic graft rejections were observed in eight and three patients, respectively. Twenty-one patients (42%) reported ADRs. C0 and AUC0-12h, showed a significant difference between CYP3A5*1 carriers (mean C0=4 ng.mL-1 and AUC0-12h=94.37 ng.h.mL-1) and CYP3A5*3/3 or poor metabolizers carriers (mean C0=7.45 ng.mL-1; AUC0-12h=151.27 ng.h.mL-1) (p=0.0001; p=0.003, respectively). Supratherapeutic tacrolimus levels were significantly more common in poor metabolizers (p=0.046; Odds-ratio =1.3; confidence interval 95% [1.12-1.66]). The impact of SNP was significant on C0, AUC0-12h, C0/Dose and AUC0-12h/Dose, only in the late phase (p=0.01, 0.002, 0.012, 0.003 respectively). Conclusion: CYP3A5*3 variant was significantly associated with tacrolimus pharmacokinetics but had no impact on graft outcomes. |
| المشرفين على المادة: | WM0HAQ4WNM (Tacrolimus) 0 (Immunosuppressive Agents) EC 1.14.14.1 (Cytochrome P-450 CYP3A) EC 1.14.14.1 (CYP3A5 protein, human) |
| تواريخ الأحداث: | Date Created: 20240311 Date Completed: 20240312 Latest Revision: 20240312 |
| رمز التحديث: | 20240312 |
| PMID: | 38465753 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 2724-7031 |
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