The effects of the CYP3A5*3 variant on tacrolimus pharmacokinetics and outcomes in Tunisian kidney transplant recipients Section Original articles


Rim charfi
Mohamed Mongi Bacha
Myriam Ben Fadhla
Khouloud Ferchichi
Hanene El Jebari
Emna Gaies
Anis Klouz
Ezzeddine Abderrahim
Fathi Ben Hamida
Taieb Ben Abdallah
Sameh Trabelsi
Yosr Gorgi
Imen Sfar


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.


Adverse drug reaction, kidney grafting, pharmacokinetics, rejection, SNPS, tacrolimus


Author Biography

Rim charfi, Department of clinical pharmacology, National Centre Chalbi Belkahia of Pharmacovigilance, Research Laboratory of Clinical and Experimental Pharmacology (LR16SP02), Faculty of de Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia



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