Pharmacokinetic study of methylnaltrexone after single and multiple subcutaneous administrations in healthy Chinese subjects.

1. Pharmacokinetics of methylnaltrexone (MNTX) were evaluated after subcutaneous administrations (s.c.) in healthy Chinese subjects. 2. In a cross-over single dose study, 12 subjects were given 0.075, 0.15, and 0.3 mg/kg of MNTX bromide injection. In a multiple doses study, another 12 subjects subcutaneously received 0.15 mg/kg of MNTX bromide injection every 48 h, in total five administrations. The concentrations of MNTX in plasma were quantified by LC-MS/MS. 3. After single s.c. administrations of 0.075, 0.15, and 0.3 mg/kg of MNTX bromide, C values of MNTX were 93.5 ± 28.6, 191 ± 37, and 364 ± 54 ng/mL, respectively, and AUC were 88.8 ± 8.8, 181 ± 16, and 357 ± 34 ng⋅h/mL, respectively. The t of MNTX was about 7.7 h. After multiple doses administration, the C, C, AUC, and MRT values were 191 ± 50, 3.79 ± 0.40 ng/mL, 182 ± 19 ng⋅h/mL, and 3.56 ± 1.17 h, respectively. 4. Methylnaltrexone bromide displayed dose-proportional pharmacokinetics in the dose range of 0.075-0.3 mg/kg. After multiple doses administration, t was slightly prolonged, with the cumulative factor of 1.02. This study provides a pharmacokinetic reference after a single dose and multiple doses of MNTX bromide in Chinese subjects.