OBJECTIVES: To evaluate the effect of a low- and high-fat meal and co-administration of ranitidine or omeprazole on the pharmacokinetics of ritonavir-boosted danoprevir (DNVr). METHODS: In this randomised, open-label, cross-over study, healthy subjects received a single dose of DNVr. In group 1, DNVr was administered while fasting or with a low-fat or high-fat meal. In group 2, DNVr was administered alone or with ranitidine 150 mg (single dose) or omeprazole 40 mg (multiple doses). KEY FINDINGS: Group 1 (n = 16): relative to fasting conditions, food slightly prolonged absorption but did not alter the extent of absorption. DNV area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞), maximum plasma concentration (C(max)), and plasma concentration 12 h after administration (C12h) geometric mean ratios (GMR%) (90% confidence interval (CI)) with a low-fat meal were 92.3 (80.2-106), 61.8 (51.0-74.9) and 95.2 (80.9-112), versus fasting conditions, and with a high-fat meal 99.5 (86.4-115), 58.9 (48.5-71.6) and 101 (86.0-119). Group 2 (n = 13): ranitidine or omeprazole had no clinically significant effect on DNV pharmacokinetics. DNV AUC0-∞, Cmax and C12h GMR% (90% CI) with ranitidine: 81.9 (68.3-98.1), 104 (86.9-123) and 87.5 (69.3-111), and with omeprazole: 83.0 (67.4-102), 92.7 (70.6-122) and 93.3 (65.6-133). CONCLUSIONS: The absence of clinically relevant effects of food, ranitidine or omeprazole on DNVr pharmacokinetics suggests that DNVr can be administered without regard to meals and in combination with H2 antagonists or proton pump inhibitors.
RCT Entities:
OBJECTIVES: To evaluate the effect of a low- and high-fat meal and co-administration of ranitidine or omeprazole on the pharmacokinetics of ritonavir-boosted danoprevir (DNVr). METHODS: In this randomised, open-label, cross-over study, healthy subjects received a single dose of DNVr. In group 1, DNVr was administered while fasting or with a low-fat or high-fat meal. In group 2, DNVr was administered alone or with ranitidine 150 mg (single dose) or omeprazole 40 mg (multiple doses). KEY FINDINGS: Group 1 (n = 16): relative to fasting conditions, food slightly prolonged absorption but did not alter the extent of absorption. DNV area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞), maximum plasma concentration (C(max)), and plasma concentration 12 h after administration (C12h) geometric mean ratios (GMR%) (90% confidence interval (CI)) with a low-fat meal were 92.3 (80.2-106), 61.8 (51.0-74.9) and 95.2 (80.9-112), versus fasting conditions, and with a high-fat meal 99.5 (86.4-115), 58.9 (48.5-71.6) and 101 (86.0-119). Group 2 (n = 13): ranitidine or omeprazole had no clinically significant effect on DNV pharmacokinetics. DNV AUC0-∞, Cmax and C12h GMR% (90% CI) with ranitidine: 81.9 (68.3-98.1), 104 (86.9-123) and 87.5 (69.3-111), and with omeprazole: 83.0 (67.4-102), 92.7 (70.6-122) and 93.3 (65.6-133). CONCLUSIONS: The absence of clinically relevant effects of food, ranitidine or omeprazole on DNVr pharmacokinetics suggests that DNVr can be administered without regard to meals and in combination with H2 antagonists or proton pump inhibitors.
Authors: Barbara J Brennan; Agnès Poirier; Sebastian Moreira; Peter N Morcos; Petra Goelzer; Renée Portmann; Jiney Asthappan; Christoph Funk; Patrick F Smith Journal: Clin Pharmacokinet Date: 2015-05 Impact factor: 6.447