A Review of Population Pharmacokinetic Models and Dosing Algorithms Assessing the Influence of CYP3A5 Genotype and Other Clinical Covariates on Tacrolimus Pharmacokinetics.

CYP3A5 normal/intermediate metabolisers show increased clearance (median 1.64-fold) versus poor metabolisers, requiring a dose increase.

Review of 68 tacrolimus population pharmacokinetic models assessing the influence of CYP3A5 genotype and other covariates. CYP3A5 genotype was the most frequently retained covariate on clearance (88 % of models), ahead of body size, haematocrit and time since transplant. Normal/intermediate metabolisers had a median apparent clearance 1.64-fold higher than poor metabolisers. The authors conclude that a substantial dose increase (about 75 %) is required in normal/intermediate metabolisers, and quantify the effect of azoles, Wuzhi capsules and corticosteroids.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

This quantitative synthesis supports the CPIC recommendation for CYP3A5 genotype-guided tacrolimus dosing while quantifying the magnitude of adjustment (~75 %) and the effect of concomitant interactions. Valuable for standardising dosing algorithms in transplantation, though the heterogeneity of the 68 models warrants cautious interpretation.

Analysis by Dr Thibaut Benquey