A randomized, double-blind, pharmacokinetic study of oral maribavir with tacrolimus in stable renal transplant recipients.

Abstract

Maribavir is being developed as a novel agent for the prevention or treatment of cytomegalovirus infections after stem cell and organ transplantation. This was a randomized, double-blind, placebo-controlled study designed to evaluate the potential pharmacokinetic interaction of concomitant administration of maribavir and tacrolimus. Twenty-five adult renal transplant recipients with stable renal function and stable dosing regimens of tacrolimus were randomized (20 maribavir 400 mg p.o. q12 h: 5 placebo). Tacrolimus whole blood concentration profiles were determined before and after 7 days of co-administration with maribavir. When co-administered with maribavir, tacrolimus mean C(max) increased 38%, tacrolimus trough concentrations (12 h post-dose) increased 57% and tacrolimus AUC((0-tau)) increased 51%. Apparent oral clearance of tacrolimus decreased 34% and T(max) was delayed by 0.5 h. There were no serious adverse events and no subject prematurely discontinued treatment. Because of the limited 7-day dosing course, the adverse event profile could not be adequately assessed. However, as seen with other maribavir studies, dysgeusia was common (90% of maribavir subjects and 20% of placebo subjects). In conclusion, co-administration of maribavir 400 mg twice daily increases exposure to tacrolimus. Routine therapeutic drug monitoring of tacrolimus blood concentrations should be included both at initiation and completion of maribavir treatment.

• Authors: M D Pescovitz, R Bloom, J Pirsch, J Johnson, S Gelone, S A Villano
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 9 Issue 10 Pg. 2324-30 (Oct 2009) ISSN: 1600-6143 [Electronic] United States
• PMID: 19663892 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Benzimidazoles
• Immunosuppressive Agents
• Placebos
• Ribonucleosides
• maribavir
• Tacrolimus

Topics

• Administration, Oral
• Adult
• Area Under Curve
• Benzimidazoles (administration & dosage, pharmacokinetics, therapeutic use)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Immunosuppressive Agents (administration & dosage, pharmacokinetics, therapeutic use)
• Kidney Transplantation
• Male
• Middle Aged
• Placebos
• Ribonucleosides (administration & dosage, pharmacokinetics, therapeutic use)
• Tacrolimus (administration & dosage, therapeutic use)