Excretion and metabolism of milnacipran in humans after oral administration of milnacipran hydrochloride.
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Li F, Chin C, Wangsa J, Ho J
Excretion and metabolism of milnacipran in humans after oral administration of milnacipran hydrochloride.
Drug Metab Dispos. 2012 Sep;40(9):1723-35. doi: 10.1124/dmd.112.045120. Epub 2012 May 31.
- PubMed ID
- 22653299 [ View in PubMed]
- Abstract
The pharmacokinetics, excretion, and metabolism of milnacipran were evaluated after oral administration of a 100-mg dose of [(1)(4)C]milnacipran hydrochloride to healthy male subjects. The peak plasma concentration of unchanged milnacipran ( approximately 240 ng/ml) was attained at 3.5 h and was lower than the peak plasma concentration of radioactivity ( approximately 679 ng Eq of milnacipran/ml) observed at 4.3 h, indicating substantial metabolism of milnacipran upon oral administration. Milnacipran has two chiral centers and is a racemic mixture of cis isomers: d-milnacipran (1S, 2R) and l-milnacipran (1R, 2S). After oral administration, the radioactivity of almost the entire dose was excreted rapidly in urine (approximately 93% of the dose). Approximately 55% of the dose was excreted in urine as unchanged milnacipran, which contained a slightly higher proportion of d-milnacipran ( approximately 31% of the dose). In addition to the excretion of milnacipran carbamoyl O-glucuronide metabolite in urine ( approximately 19% of the dose), predominantly as the l-milnacipran carbamoyl O-glucuronide metabolite ( approximately 17% of the dose), approximately 8% of the dose was excreted in urine as the N-desethyl milnacipran metabolite. No additional metabolites of significant quantity were excreted in urine. Similar plasma concentrations of milnacipran and the l-milnacipran carbamoyl O-glucuronide metabolite were observed after dosing, and the maximum plasma concentration of l-milnacipran carbamoyl O-glucuronide metabolite at 4 h after dosing was 234 ng Eq of milnacipran/ml. Lower plasma concentrations (<25 ng Eq of milnacipran/ml) of N-desethyl milnacipran and d-milnacipran carbamoyl O-glucuronide metabolites were observed.