2005•Clinical Pharmacology & TherapeuticsRequires access
Effect of the anti-cytomegalovirus (CMV) drug maribavir (MB) on the activities of cytochrome p450 (CYP) 1A2, 2C9, 2C19, 2D6, 3A, N-ACETYLTRANSFERASE-2 (NAT-2), and xanthine oxidase (XO) as assessed by the cooperstown 5+1 drug cocktail
Jian‐Gong Ma, A NAFZIGER, Stephen Villano, A GAEDIGK, Jennifer Victory, Joseph Bertino
Open publisher page 1 citations
Abstract
Background The effect of repeated dose oral MB on CYP1A2, 2C9, 2C19, 2D6, 3A, NAT-2, and XO activity were evaluated in healthy volunteers. Methods A drug interaction study was conducted with 20 (16 MB, 4 placebo) healthy nonsmoking adults (10 women). Genotypic EMs were given by mouth, 2 mg/kg caffeine (CYP1A2, NAT-2, XO), 10 mg warfarin (W)+ 10 mg vitamin K (CYP2C9), 40 mg omeprazole (OMP) (CYP2C19), 30 mg dextromethorphan (DM) (CYP2D6), and 0.075 mg/kg midazolam (MDZ) (CYP3A) 4 days before (day −4) and after 7 days (day 7) of 400 mg MB twice daily (continued for 10 days). Biomarker measurements (urinary or plasma metabolic ratios, plasma AUC or total body CL) were determined. Least squares geometric mean ratios (LS-GMR) and 90% confidence intervals (90% CI) were calculated. Results (see Table) Conclusions Repeated dose MB may decrease CYP2C19 and CYP2D6 activity, although the clinical significance of the effect remains to be determined. No effect was observed on CYP1A2, 2C9, 3A, NAT-2, or XO. These results will guide further evaluation of the drug-drug interaction potential for MB. Clinical Pharmacology & Therapeutics (2005) 77, P19–P19; doi: 10.1016/j.clpt.2004.11.075 Parameter N LS-GMR Day7/Day-4 90% CI CYP1A2 (1X + 1U + AFMU/17U) 15 0.86 0.80–0.92 CYP2C9 (W AUC0-∞) 16 1.01 0.95–1.07 CYP2C19 (OMP/5-OH) 16 1.71 1.50–1.92* CYP2D6 (DM/DX) 16 1.18 0.94–1.41* CYP3A (MDZ CL/F) 16 1.13 1.01–1.24 NAT-2 (AFMU/1X + 1U) 15 0.96 0.86–1.06 XO (1U/1X + 1U) 15 1.02 1.00–1.04 * 90 CI outside the 0.8–1.25 interval indicates that equivalence was not demonstrated