PRECISION MEDICINE IN RENAL TRANSPLANT PATIENTS - ROLE OF ABCG2 LOSS OF FUNCTION POLYMORPHISM (CROSBI ID 724227)
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Podaci o odgovornosti
Borić Bilušić, Ana ; Božina, Nada ; Lalić, Zdenka ; Lovrić, Mila ; Nađ-Škegro, Sandra ; Penezić, Luka ; Barišić, Karmela ; Trkulja, Vladimir
engleski
PRECISION MEDICINE IN RENAL TRANSPLANT PATIENTS - ROLE OF ABCG2 LOSS OF FUNCTION POLYMORPHISM
Introduction: Breast cancer resistance protein (BCRP/ABCG2) is an efflux transporter important in pharmacokinetics of a number of drugs. We evaluated effect of a loss-of-function polymorphism ABCG2 c.421C>A on exposure to mycophenolic acid (MPA) in stable adult renal transplant recipients of Croatian origin. Materials and methods: Patients (n=68 ; 43 co-treated with cyclosporine, 25 with tacrolimus) were genotyped for ABCG2 c.421C>A and 11 polymorphisms in genes encoding enzymes and transporters implicated in MPA pharmacokinetics. Donors were genotyped for polymorphisms suggested to affect renal MPA secretion. ABCG2 c.421C>A variant vs. wild-type (wt) patients were matched in respect to demographic, biopharmaceutic and genetic variables (full optimal combined with exact matching) and compared for dose-adjusted steady-state MPA pharmacokinetics (Frequentist and Bayes [skeptical neutral prior] estimates of geometric means ratios, GMR). Results: Raw data (12 variant vs. 56 wt patients) indicated by around 40% higher total exposure (frequentist GMR=1.45, 95%CI 1.10-1.91 ; Bayes = 1.38, 95%CrI 1.07-1.81) and by around 30% lower total body clearance (frequentist GMR=0.66, 0.58-0.90 ; Bayes=0.71, 0.53-0.95) in variant carriers than in wt controls. The estimates were similar in matched data (11 variant vs. 43 wt patients): exposure GMR=1.41 (1.11-1.79) frequentist, 1.39 (1.15-1.81) Bayes, with 85.5% probability of GMR >1.20 ; clearance GMR=0.73 (0.58-0.93) frequentist, 0.71 (0.54-0.95) Bayes. Raw data indicated exposure difference in tacrolimus-treated but not in cyclosporine-treated patients (P for genotype-calcineurin type interaction 0.045 frequentist, 92.7% Bayes). Conclusions: Loss-off-function polymorphism ABCG2 c.421C>A increases steady-state exposure to MPA in stable renal transplant patients. The effect might be conditional on the type of calcineurin inhibitor.
precision medicine, breast cancer resistance protein, transplant recipients, mycophenolic acid
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Podaci o prilogu
121-121.
2022.
nije evidentirano
objavljeno
Podaci o matičnoj publikaciji
Pharmaca
Mršić-Pelčić, Jasenka ; Vitezić, Dinko ; Janković, Tamara
Zagreb:
0031-6857
Podaci o skupu
10. hrvatski kongres farmakologije ; 1. hrvatski kongres kliničke farmakologije s međunarodnim sudjelovanjem = 10th Croatian Congress of Pharmacology ; 1st Croatian Congress of Clinical Pharmacology and Therapeutics with International Participation
predavanje
22.09.2022-25.09.2022
Opatija, Hrvatska