Personalizing initial calcineurin inhibitor dosing by adjusting to donor CYP3A-status in liver transplant patients.

摘要: AIMS Inter-individual variability in dose requirements of calcineurin inhibitors (CNI) has been linked to genetic polymorphisms CYP3A enzymes. CYP3A5*3, CYP3A4*1B and CYP3A4*22 alleles liver grafts may explain about one third the inter-individual differences pharmacokinetics ciclosporin tacrolimus recipients. However, non-genetic factors, influencing expression, can contribute function due phenoconversion. The present study evaluated association between CYP3A4 expression combined with CYP3A5 genotype donor livers recipients' CNI therapy after transplantation. METHODS contribution donors' blood concentrations CNIs was 131 transplant RESULTS recipients from normal expresser donors carrying CYP3A5*3/*3 required maintenance doses more or less similar bodyweight-controlled starting (9.1 mg kg(-1) 0.1 tacrolimus). patients transplanted low expressers substantial reduction (by 50%, 4.2 ciclosporin, 0.047 tacrolimus, P < 0.001), while high at least copy functional CYP3A5*1 allele an increase 50% [12.8-13.8 kg(-1)] for 100% [0.21 ] 0.001) initial achieving target concentrations. CONCLUSIONS Donor livers' CYP3A-status, taking both allelic variations into account, better identify risk over- underexposure, avoidance misdosing-induced graft injury early post-operative period.