title: 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.
  
  
  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). Tmax was 180 min, C(max) was 1083.7 ± 293.9 ng/mL, and T(½) 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(½) was 259 min. The AUC₀₋₅₄₀ 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.
  
  
  CONCLUSIONS
  MNTX-PC formulation significantly enhanced the oral bioavailability of MNTX.
authors: Department of Pharmaceutics, School of Pharmaceutical Science, Yantai University , Yantai , China.
authors: Dong-Hai
authors: DH
authors: Lin
authors: Chong-Zhi
authors: CZ
authors: Wang
authors: Li-Fang
authors: LF
authors: Qin
authors: Xin-Xin
authors: XX
authors: Xie
authors: Jun-Teng
authors: JT
authors: Wang
authors: Maojian
authors: M
authors: Gu
authors: Eryn
authors: E
authors: McEntee
authors: Chun-Su
authors: CS
authors: Yuan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D010713:Phosphatidylcholines / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014961:X-Ray Diffraction
chemical_list: D009292:Narcotic Antagonists; D010713:Phosphatidylcholines; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone