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

Abstract

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_max values of MNTX were 93.5 ± 28.6, 191 ± 37, and 364 ± 54 ng/mL, respectively, and AUC_0–∞ were 88.8 ± 8.8, 181 ± 16, and 357 ± 34 ng⋅h/mL, respectively. The t_1/2 of MNTX was about 7.7 h. After multiple doses administration, the C_max, C_av, AUC_ss, and MRT_0–∞ 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_1/2 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.

Keywords:

• Chinese subjects
• methylnaltrexone
• multiple doses
• pharmacokinetics
• single dose
• subcutaneous injection