Absorption, distribution, metabolism and excretion of [14C]dexlansoprazole in healthy male subjects.
Clin Drug Investig
; 32(5): 319-32, 2012 May 01.
Article
in En
| MEDLINE
| ID: mdl-22455762
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 60 mg 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.
Full text:
1
Database:
MEDLINE
Main subject:
Aryl Hydrocarbon Hydroxylases
/
2-Pyridinylmethylsulfinylbenzimidazoles
/
Proton Pump Inhibitors
Limits:
Adolescent
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Adult
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Humans
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Male
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Middle aged
Language:
En
Year:
2012
Type:
Article