Enhancing Oral Bioavailability of Methylnaltrexone Using an Emulsion Formulation Academic Article uri icon


  • Methylnaltrexone (MNTX) is a peripherally-acting opioid receptor antagonist. Since it has restricted access to the blood-brain barrier, MNTX has the ability to decrease opioid-induced constipation without affecting the analgesic effects of opioid pain medications. MNTX has a limited gastrointestinal absorption and currently, only subcutaneous MNTX is clinically available to help restore bowel function in patients with late-stage advanced illness who are receiving opioids. A MNTX emulsion (MNTX-EM) formulation was prepared in this study to improve the oral bioavailability of the compound. A sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was established and validated for the determination of MNTX plasma concentrations. With an extended linear range of 1 to 1000 ng/mL, this assay was specific, precise, and accurate. Following 110 mg/kg oral administrations of unformulated methylnaltrexone water solution (MNTX-WS) and MNTX-EM in rats, plasma samples were collected for up to 9 h and MNTX levels were measured. The plasma MNTX concentrations after MNTX-WS and MNTX-EM were compared. Data showed that there were two MNTX concentration peaks after both MNTX-WS and MNTX-EM. For the first peak, the peak plasma concentration (Cmax) and the area under the concentration curve (AUC) from 0 to 60 min for MNTX-WS and MNTX-EM were 210.0 ng/mL, 87.2 ngh/mL and 390.2 ng/mL, 321.9 ngh/mL, respectively (both P < 0.01). For the second peak, Cmax and AUC from 60 to 420 min for MNTX-WS and MNTX-EM were 172.7 ng/mL, 663.4 ngh/mL and 597.6 ng/mL, 1941.7 ngh/mL, respectively (both P < 0.01). The relative bioavailability after oral administration of MNTX-EM was 302% compared to that of MNTX-WS. These results suggested that the emulsion formulation might be clinically useful in enhancing the oral absorption of MNTX. 2011 Bentham Science Publishers Ltd.

published proceedings

  • Letters in Drug Design & Discovery

author list (cited authors)

  • Yu, L., Lu, W., Xiang, P., Wang, L., Chen, L. i., Chen, T., ... Yuan, C.

citation count

  • 4

complete list of authors

  • Yu, Li-Fang||Lu, Wei-Gen||Xiang, Ping||Wang, Li-Li||Chen, Li||Chen, Ting-Ting||Maojian Gu, Michael||Wang, Chong-Zhi||Yuan, Chun-Su

publication date

  • January 2011