Naslov
PRECISION MEDICINE IN RENAL TRANSPLANT PATIENTS - ROLE OF ABCG2 LOSS OF FUNCTION POLYMORPHISM

Autori
Borić Bilušić, Ana ; Božina, Nada ; Lalić, Zdenka ; Lovrić, Mila ; Nađ-Škegro, Sandra ; Penezić, Luka ; Barišić, Karmela ; Trkulja, Vladimir

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Pharmaca, Glasilo hrvatskog društva za kliničku farmakologiju i terapiju / Mršić-Pelčić, Jasenka ; Vitezić, Dinko ; Janković, Tamara - Zagreb, 2022, 121-121

Skup
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

Mjesto i datum
Opatija, Hrvatska, 22.09.2022. - 25.09.2022

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
precision medicine, breast cancer resistance protein, transplant recipients, mycophenolic acid

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti, Farmacija

POVEZANOST RADA