How to handle missed or delayed doses of tacrolimus in renal transplant recipients? A pharmacokinetic investigation

Pharmacological Research : the Official Journal of the Italian Pharmacological Society
Franck Saint-MarcouxPierre Marquet

Abstract

Every transplant patient will, at least occasionally, miss immunosuppressive drug doses or take them outside the prescribed times. This study aims at quantifying the impact of poor execution on tacrolimus exposure in renal transplant patients. Validated pharmacokinetic tools applied in clinical setting were used to simulate the steady-state pharmacokinetic profiles of the drug when given as the immediate-release formulation to renal transplant patients, being CYP3A5 expressors or not, and who have reached either a standard or a minimized exposure. Situations of interruption due to a missed or delayed dose were simulated and the impact on drug exposure was explored. In case of a missed dose, it was observed that: (i) a single forgotten dose can greatly impact exposure: up to 49% decrease for tacrolimus trough concentration and 70% for AUC0-12 h in patients with the highest clearance values; (ii) patients with a minimized exposure are the most affected by a missed dose; and (iii) a dose of 1.5 times the usual dose may be recommended after a total dose oversight. Considering that intra-patient exposure variability is a predictive factor of poor graft outcome, these modeling results may serve as recommendations for patients, both p...Continue Reading

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Citations

Sep 27, 2018·Transplant International : Official Journal of the European Society for Organ Transplantation·Erlend Johannessen EgelandAnders Åsberg
Feb 17, 2019·Transplant International : Official Journal of the European Society for Organ Transplantation·Marte Theie GustavsenAnders Åsberg
Dec 4, 2019·European Journal of Drug Metabolism and Pharmacokinetics·Jia-Qin GuGuo-Fu Li
Oct 20, 2019·Transplantation Reviews·Sumit R M GokoelJohan W de Fijter

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