- Prof. Van Gelder Teun
CV
ABSTRACT
The immunosuppressive drugs used in solid organ transplantation have narrow therapeutic ranges and highly variable pharmacokinetics between individuals. The most frequently prescribed drug is tacrolimus, of which the exposure strongly correlates with the expression and activity of the metabolizing enzymes cytochrome P450 (CYP) 3A4 and CYP3A5. These enzymes are polymorphically expressed, which is in part explained by the presence of single-nucleotide polymorphisms in the CYP3A4 and CYP3A5 genes. There are striking differences in the prevalence of the different genotypes among patients with varying ethnicity. The higher dose requirement of patients expressing CYP3A5 may cause a delay in reaching the desired tacrolimus target concentrations, potentially with reduced efficacy as a result. The question is whether the implementation of pre-transplantation genotyping will benefit patient management.