The evaluation of potential pharmacokinetic interaction between sirolimus and tacrolimus in healthy volunteers.
Tortorici MA, Parks V, et al.European Journal of Clinical Pharmacology [record in progress]
Aims
Firstly, to assess a possible pharmacokinetic interaction between sirolimus and tacrolimus in healthy volunteers. Secondly, to evaluate the safety and tolerability of the combination of sirolimus and tacrolimus.
Interventions
A four-way crossover design was used to compare the following four interventions: sirolimus as a single 15-mg dose versus tacrolimus as a single 10-mg dose versus sirolimus as a single 15-mg oral dose and tacrolimus as a single 10-mg oral dose administered together versus tacrolimus as a single 10-mg oral dose and 4 h later, sirolimus as a single 15-mg oral dose.
Participants
28 white male healthy volunteers
Outcomes
Pharmacokinetic parameters included maximal concentration (Cmax), time to maximal concentration (Tmax), elimination half-life (t½), area under the concentration–time curve from 0 h to infinity (AUCinf), apparent oral clearance (CL/F) and apparent volume of distribution at steady state (Vss/F). Safety measures included adverse event (AE) monitoring, vital signs, 12-lead electrocardiogram (ECG) recordings and clinical laboratory tests.
Follow-up
13 weeks
CET Conclusions
In this study of a possible interaction between sirolimus and tacrolimus in healthy volunteers, there was no evidence of any clinically important drug interaction between sirolimus and tacrolimus after single dose administration. However other factors in clinical practice, such as anti rejection treatment, might alter any possible interaction.
Data analysis
Per protocol analysis
Trial registration
Not reported