Single and multiple dose pharmacokinetics (PK) of maribavir (MB) in healthy adults

Abstract

Background MB is an oral antiviral agent with activity against cytomegalovirus (CMV). Single and multiple dose PK of MB were examined in healthy adults as part of a drug interaction study. Methods This was a double blind, placebo-controlled study. 20 (16 MB, 4 placebo) nonsmoking, men and women (10 women) between the ages of 18 and 55 years of age were included. Subjects were given 400 mg oral MB twice daily for 10 days. 9 blood samples were collected from 0 to 12 hr after MB administration on Day 1 (single dose) and Day 10 (multiple dose). MB concentrations were analyzed by LC/MS/MS. MB PK parameters were determined using noncompartmental analysis with WinNonlin® 4.1. Safety was assessed by physical exam, clinical labs, ECGs, and adverse events. Results Data (n=16) are presented as arithmetic means (SD): (see Table) The geometric mean AUCratio (Day 10 AUC0-Tau/Day 1 AUC0-Tau) was 1.12 (0.68, 1.84). All subjects completed dosing. Oral MB was safe and well tolerated; taste disturbance was the most frequently reported adverse event. Conclusions MB was absorbed orally, with predicted steady state reached after the first dose. Accumulation at steady state was minimal. Clinical evaluation of the anti-CMV activity of MB in the transplant setting is ongoing. Clinical Pharmacology & Therapeutics (2005) 77, P19–P19; doi: 10.1016/j.clpt.2004.11.074 Table 1. PK parameters (units) Day 1 MB PK Day 10 MB PK Cmax (ng/mL) 15682 (4984) 16646 (5826) AUC0-Tau (ng*hr/mL) 82410 (25916) 89912 (41171) Vz/F (mL) 24018 (7418) 24894 (6387) CL/F (mL/hr) 4791 (2017) 5295 (2277) t1/2 (hr) 3.7 (0.9) 3.6 (1.1)