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Absorption, Distribution, Metabolism and Excretion of [14C]Dexlansoprazole in Healthy Male Subjects

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Abstract

Background and Objective: The proton pump inhibitor dexlansoprazole is a modified-release formulation of dexlansoprazole, an enantiomer of lansoprazole, which employs a Dual Delayed Release™ (DDR) delivery system. This study was conducted in healthy subjects to assess the absorption, distribution, metabolism and excretion of a 60mg dose of [14C]dexlansoprazole.

Methods: After multiple daily doses of dexlansoprazole DDR for 4 days followed by a single dose of [14C]dexlansoprazole on day 5, absorption, distribution, metabolism and elimination of [14C]dexlansoprazole were assessed in six healthy male subjects whose CYP (cytochrome P450) 2C19 metabolizer status was also determined.

Results: Five subjects were phenotyped as extensive metabolizers (EMs) and one subject was a poor metabolizer (PM). Recovery of radioactivity in urine and faeces averaged 98% after 7 days (51% in urine and 48% in faeces) post-14C dosing. In plasma, dexlansoprazole was the largest component detected, with the main metabolites in the EM subjects being 5-glucuronyloxy dexlansoprazole and 5-hydroxy dexlansoprazole (CYP2C19 mediated), whereas the PM subject had greater amounts of dexlansoprazole sulfone (CYP3A mediated). Dexlansoprazole was not detected in urine; six metabolites were identified accounting for an average of 86% of the urinary radioactivity, with 5-glucuronyloxy dexlansoprazole, 5-glucuronyloxy dexlansoprazole sulfide, 2-S-N-acetylcysteinyl benzimidazole and 5-sulfonyloxy dexlansoprazole sulfide being the primary metabolites. In faeces, parent drug and six identified metabolites accounted for 23% and 72%, respectively, of the faecal radioactivity, with 5-hydroxy dexlansoprazole sulfide and dexlansoprazole sulfide being predominant.

Conclusion: Overall, the results indicate that [14C]dexlansoprazole was well absorbed and extensively metabolized by oxidation, reduction and conjugation to 13 identified metabolites.

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Acknowledgements

This study (T-P106-141) was presented at the 15th biennial meeting of the International Society for the Study of Xenobiotics-North America 2008, San Diego, CA, USA. The authors would like to thank John Brackett, PhD, of Takeda Global Research & Development Center, Inc, for formulation development of the radiolabelled dexlansoprazole in Maalox®. This study was sponsored by Takeda Global Research & Development Center, Inc, Deerfield, IL, USA. The study was conducted by TAP Pharmaceutical Products, Inc, which is now a part of Takeda Global Research & Development Center, Inc. The study sponsor was involved in the design and conduct of the study and collection and management of the data. Ronald Lee is an employee of Takeda Global Research & Development Center, Inc, and Brian Grabowski was an employee of Takeda Global Research & Development Center, Inc, at the time the study was conducted. Both authors were involved in the design of the study, analysis and interpretation of the data, and the preparation, review and approval of this manuscript. Assistance in manuscript preparation was provided by Meryl Gersh, PhD, of AlphaBioCom, LLC, King of Prussia, PA, and funded by Takeda Pharmeceuticals USA, Inc.

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  1. Takeda Global Research & Development Center, Inc, One Takeda Parkway, Deerfield, IL, 60015, USA

    Brian Grabowski & Ronald D. Lee PhD

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  1. Brian Grabowski
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Correspondence to Ronald D. Lee PhD.

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Grabowski, B., Lee, R.D. Absorption, Distribution, Metabolism and Excretion of [14C]Dexlansoprazole in Healthy Male Subjects. Clin Drug Investig 32, 319–332 (2012). https://doi.org/10.2165/11630930-000000000-00000

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