A published pharmacogenetic algorithm was poorly predictive of tacrolimus clearance in an independent cohort of renal transplant recipients
Article first published online: 20 AUG 2013
© 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society
British Journal of Clinical Pharmacology
Special Issue: Cancer Therapeutics Themed Section
Volume 76, Issue 3, pages 425–431, September 2013
How to Cite
Boughton, O., Borgulya, G., Cecconi, M., Fredericks, S., Moreton-Clack, M. and MacPhee, I. A. M. (2013), A published pharmacogenetic algorithm was poorly predictive of tacrolimus clearance in an independent cohort of renal transplant recipients. British Journal of Clinical Pharmacology, 76: 425–431. doi: 10.1111/bcp.12076
- Issue published online: 20 AUG 2013
- Article first published online: 20 AUG 2013
- Accepted manuscript online: 11 JAN 2013 06:34AM EST
- Manuscript Accepted: 29 DEC 2012
- Manuscript Received: 23 MAY 2012
- dosing algorithm;
- renal transplant;
An algorithm based on the CYP3A5 genotype to predict tacrolimus clearance to inform the optimal initial dose was derived using data from the DeKAF study (Passey et al. Br J Clin Pharmacol 2011; 72: 948–57) but was not tested in an independent cohort of patients. Our aim was to test whether the DeKAF dosing algorithm could predict estimated tacrolimus clearance in renal transplant recipients at our centre.
Predicted tacrolimus clearance based on the DeKAF algorithm was compared with dose-normalized trough whole-blood concentrations (estimated clearance) on day 7 after transplantation in a single-centre cohort of 255 renal transplant recipients.
There was a weak correlation (r = 0.431) between clearance based on dose-normalized trough whole-blood concentrations and DeKAF algorithm-predicted clearance. The means of the tacrolimus clearance predicted by the DeKAF algorithm and the estimated tacrolimus clearance based on the dose-normalized trough blood concentrations were plotted against the differences in the clearance as a Bland–Altman plot. Logarithmic transformation was performed owing to the increased difference in tacrolimus clearance as the mean clearance increased. There was a highly significant systematic error (P < 0.0005) characterized by a sloped regression line [gradient, 0.88 (95% confidence interval, 0.75–1.01)] on the Bland–Altman plot.
The DeKAF algorithm was unable to predict the estimated tacrolimus clearance accurately based on real tacrolimus doses and blood concentrations in our cohort of patients. Other genes are known to influence the clearance of tacrolimus, and a polygenic algorithm may be more predictive than those based on a single genotype.