3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

PHARMACOKINETICS OF TMC114: EFFECT OF OMEPRAZOLE AND RANITIDINE

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. WePe3.3C13

Sekar V.¹, Hoetelmans R.², De Marez T.¹, De Pauw M.², Vangeneugden T.², Godderis F.², Parys W.¹, Lefebvre E.^1
1Tibotec Inc., Yardley, PA, United States of America, ²Tibotec Inc., Mechelen, Belgium

INTRODUCTION: TMC114 is a new protease inhibitor (PI) with potent in vitro activity against wild-type HIV and many viruses resistant against currently licensed PIs. TMC114 is currently developed for co-administration with low-dose RTV. To evaluate the effect of omeprazole and ranitidine on the steady-state pharmacokinetics of TMC114 with low-dose RTV, a study was conducted in healthy volunteers.

METHODS: TMC114-C122 was an open-label, randomized, 3-way cross-over trial to investigate the effect of omeprazole and ranitidine on the pharmacokinetics of TMC114 administered with low-dose RTV. 18 healthy volunteers were randomized to receive TMC114/RTV 400/100 mg b.i.d. alone (Treatment A), in combination with 150 mg ranitidine b.i.d. (Treatment B), and in combination with 20 mg omeprazole q.d. (Treatment C). Each treatment was administered for 4 days with additional morning doses on day 5. Wash-out periods were at least 7 days. Pharmacokinetic profiles of TMC114 were determined on day 5 over 12 hours.

RESULTS: When combined with 20 mg omeprazole q.d., TMC114 AUC12h was 104% (90% CI 95.7 – 113%) compared to administration of TMC114 alone. TMC114 C_max and C0h were 101% (94.9 – 109%) and 107% (95.4 – 120%), respectively. When combined with 150 mg ranitidine TMC114 AUC12h was 95.5% (90% CI 90.4 – 101%) compared to administration of TMC114 alone. TMC114 C_max and C0h were 96.5% (89.1 – 105%) and 101% (91.6 – 112%), respectively. The overall incidence of subjects reporting an adverse event, as well as the incidence of clinical laboratory abnormalities was similar for all study treatments. The majority of adverse events were grade 1 or 2 in severity.

CONCLUSIONS: The combination of 20 mg omeprazole q.d. or 150 mg ranitidine b.i.d. with TMC114/RTV did not affect the pharmacokinetics of TMC114. The combination of omeprazole or ranitidine and TMC114/RTV was generally safe and well tolerated. No dose adjustments are necessary when TMC114 is combined with low-dose RTV and omeprazole or ranitidine.

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Clinical | WePe3.3C13 | Vanitha Sekar
Drug Interactions

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