Effect of meal and antisecretory agents on the pharmacokinetics of danoprevir/ritonavir in healthy volunteers. (10th October 2013)

• Record Type: Journal Article
• Authors: Morcos, Peter N.; Moreira, Sebastian A.; Navarro, Mercidita T.; Bech, Núria; Quatkemeyer, Amanda; Smith, Patrick F.; Brennan, Barbara J.
• Is Part Of: Journal of pharmacy and pharmacology. Volume 66:Number 1(2014:Jan.)
• Page Start: 23
• Page End: 31
• Publication Date: 2013-10-10
• Subjects: Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.12151
• Languages: English
• ISSNs: 0022-3573

Abstract

<abstract abstract-type="main"> <title>Abstract</title> <sec id="jphp12151-sec-0001" sec-type="section"> <title>Objectives</title> <p>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).</p> </sec> <sec id="jphp12151-sec-0002" sec-type="section"> <title>Methods</title> <p>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).</p> </sec> <sec id="jphp12151-sec-0003" sec-type="section"> <title>Key findings</title> <p>Group 1 (<italic>n</italic> = 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 (AUC<sub>0</sub><sub>–∞</sub>), maximum plasma concentration (<italic>C</italic><sub>max</sub>), and plasma concentration 12 h after administration (<italic>C</italic><sub>12h</sub>) 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 (<italic>n</italic> = 13): ranitidine or omeprazole had no clinically significant effect on DNV pharmacokinetics. DNV AUC<sub>0–∞</sub>, <italic>C</italic><sub>max</sub> and <italic>C</italic><sub>12h</sub> 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).</p> </sec> <sec id="jphp12151-sec-0004" sec-type="section"> <title>Conclusions</title> <p>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 H<sub>2</sub> antagonists or proton pump inhibitors.</p> </sec> </abstract>