Bioavailability of oral methylnaltrexone increases with a phosphatidylcholine-based formulation

Abstract

Objective: Methylnaltrexone (MNTX), a peripherally restricted opioid antagonist with mu-opioid receptor selectivity, can reduce opioid activity in the gastrointestinal tract while sparing the pain relief afforded by opioids. Since the bioavailability of oral MNTX is low, it is necessary to explore the oral formulations of MNTX that increase its bioavailability.

Materials and methods: An MNTX-phosphatidylcholine complex (MNTX-PC) formulation was prepared. The physicochemical properties of MNTX-PC were analyzed, and its bioavailability was evaluated in rats. After 250 mg/kg of oral MNTX-PC, plasma samples were collected up to 9 h. The concentrations of the compound in rat plasma were quantified using LC/MS/MS.

Results: Two MNTX plasma concentration peaks were observed at 120 and 180 min for the MNTX-PC group and control (MNTX in a water solution). T_max was 180 min, C_max was 1083.7 ± 293.9 ng/mL, and T_1/2 was 496 min for the MNTX-PC group. For control, T_max was 180 min, C_max was 448.4 ± 126.0 ng/mL, and T_1/2 was 259 min. The AUC_{0–540 min} for the MNTX-PC group was 5758.2 ± 1474.2 ngh/mL; for control, 1405.9 ± 447.8 ngh/mL. Thus, the relative bioavailability after the oral administration of MNTX-PC was 410% compared to that of control.

Conclusion: MNTX-PC formulation significantly enhanced the oral bioavailability of MNTX.

• Bioavailability
• constipation
• gastrointestinal absorption
• methylnaltrexone
• methylnaltrexone-phosphatidylcholine complex
• opioids
• oral formulation
• phosphatidylcholine