Dataset Information

Absorption, metabolism and excretion of opicapone in human healthy volunteers.

ABSTRACT:

Aims

The absorption, metabolism and excretion of opicapone (2,5-dichloro-3-(5-[3,4-dihydroxy-5-nitrophenyl]-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide), a selective catechol-O-methyltransferase inhibitor, were investigated.

Methods

Plasma, urine and faeces were collected from healthy male subjects following a single oral dose of 100 mg [¹⁴ C]-opicapone. The mass balance of [¹⁴ C]-opicapone and metabolic profile were evaluated.

Results

The recovery of total administered radioactivity averaged >90% after 144 hours. Faeces were the major route of elimination, representing 70% of the administered dose; 5% and 20% were excreted in urine and expired air, respectively. The C_max of total radioactivity matched that of unchanged opicapone, whereas the total radioactivity remained quantifiable for a longer period, attributed to the contribution of opicapone metabolites, involving primarily 3-O-sulfate conjugation (58.6% of total circulating radioactivity) at the nitrocatechol ring. Other circulating metabolites, accounting for <10% of the radioactivity exposure, were formed by glucuronidation, methylation, N-oxide reduction and gluthatione conjugation. Additionally, various other metabolites resulting from combinations with the opicapone N-oxide reduced form at the 2,5-dichloro-4,6-dimethylpyridine 1-oxide moiety, including nitro reduction and N-acetylation, reductive opening and cleavage of the 1,2,4-oxadiazole ring and the subsequent hydrolysis products were identified, but only in faeces, suggesting the involvement of gut bacteria.

Conclusion

[¹⁴ C]-opicapone was fully excreted through multiple metabolic pathways. The main route of excretion was in faeces, where opicapone may be further metabolized via reductive metabolism involving the 1,2,4-oxadiazole ring-opening and subsequent hydrolysis.

SUBMITTER: Loureiro AI

PROVIDER: S-EPMC9546099 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Absorption, metabolism and excretion of opicapone in human healthy volunteers.

Loureiro Ana I AI Rocha Francisco F Santos Ana T AT Singh Nand N Bonifácio Maria João MJ Pinto Rui R Kiss Laszlo E LE Soares-da-Silva Patrício P

British journal of clinical pharmacology 20220520 10

<h4>Aims</h4>The absorption, metabolism and excretion of opicapone (2,5-dichloro-3-(5-[3,4-dihydroxy-5-nitrophenyl]-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide), a selective catechol-O-methyltransferase inhibitor, were investigated.<h4>Methods</h4>Plasma, urine and faeces were collected from healthy male subjects following a single oral dose of 100 mg [<sup>14</sup> C]-opicapone. The mass balance of [<sup>14</sup> C]-opicapone and metabolic profile were evaluated.<h4>Results</h4>The recov ...[more]

PMID: 35508762

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Dataset Information

Absorption, metabolism and excretion of opicapone in human healthy volunteers.

Aims

Methods

Results

Conclusion

Publications

Absorption, metabolism and excretion of opicapone in human healthy volunteers.

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