A randomized, double-blind, pharmacokinetic study of oral maribavir with tacrolimus in stable renal transplant recipients.
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.
Pescovitz
M D
MD
Department of Surgery, Indiana University, Indianapolis, IN, USA. mpescov@iupui.edu
Bloom
R
R
Pirsch
J
J
Johnson
J
J
Gelone
S
S
Villano
S A
SA
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012263:Ribonucleosides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016559:Tacrolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D004004:Dichlororibofuranosylbenzimidazole / Q000031:analogs & derivatives
D001562:Benzimidazoles; D007166:Immunosuppressive Agents; D010919:Placebos; D012263:Ribonucleosides; D016559:Tacrolimus; C400401:maribavir; D004004:Dichlororibofuranosylbenzimidazole