Comparison of systemic exposure to nemifitide following two methods of subcutaneous administration to healthy volunteers.
The purpose of this study was to evaluate the safety and pharmacokinetics of nemifitide, a synthetic antidepressant pentapeptide, following its subcutaneous (s.c.) administration by standard needle injection or by a needle-free (Biojecttrade mark) injection and to compare these two routes of administration for systemic exposure. This small-scale, randomized, single-dose, parallel design, open-label pilot study consisted of three treatment groups of four subjects each dosed as follows: group 1: 40 mg of nemifitide administered by standard needle/syringe and groups 2 and 3: 40 and 80 mg nemifitide, respectively, administered by using a needle-free (Bioject injection delivery system. Plasma concentrations of nemifitide were determined by LC/MS/MS in blood samples collected at 10 min and 0.5, 1, 2, 4, 6 and 24 h after dosing. PK parameters, including observed C(max), T(max) and AUC(0-24), were calculated and statistical analysis of the data was conducted. Safety assessments (dosing site evaluations) were done at 0.5, 1, 5 and 24 h after dosing. Vital signs and clinical laboratory tests were taken on day 1 prior to dosing and at 24 h post-dose. Adverse experiences in all subjects were observed only as drug-related local reactions at the injection sites. All were considered mild in severity and transient (resolved by 24 h after dosing). T(max) was observed at 10 min after dose and was the same in all subjects. In the three dosing groups, 1 (40 mg), 2 (40 mg) and 3 (80 mg), observed C(max) values were 226, 245 and 440 ng/ml, respectively, and AUC(0-24) values were 108, 106 and 205 ng.h/ml, respectively. Ratios of AUC(0-24) and observed C(max) for nemifitide in plasma between groups 1 and 2 were within the 80%-125% range, indicating that the two modes of drug administration resulted in similar systemic exposure to nemifitide. Pharmacokinetic parameters (AUC(0-24) and C(max)) indicate dose-proportionality between the doses of 40 and 80 mg.