Detailed analysis of the finger-stick samples gathered during the multiple dose phase showed a strictly proportional response to dose.
Urine samples for the PK profile after the multiple dose phase were taken on day 12 at 0 4, 4 8, 8 12, 12 24, 24 36, 36 48 h after the last dose of the multiple dose phase.
Spirometry (forced expiratory volume in 1 s, FEV1) was measured before each dose of MSF during the multiple dose phase.
In the multiple dose phase, they were also conducted on days 5 and 10, before drug administration.
In the multiple dose phase AChE was assayed at the time of drug administration on days 1, 3, 5, 8, 10 and 12 (drug days).
AChE levels for detailed pharmacodynamic (PD) analysis were also determined by the method of Ellman et al. [ 12] in frozen whole blood samples taken before the first dose of the multiple dose phase (day 1) and then again on day 12 before the last dose of the multiple dose phase, 4 h later and then again on day 21 (9 days after the last dose).
A comprehensive motor examination was also conducted each morning from the first day of the single dose phase until 2 days after the final dose of the multiple dose phase.
In the multiple dose phase, these same measurements were made at the time of drug administration on days 1, 3, 5, 8, 10 and 12 and then 4 h later on days 1, 5 and 10.
AChE was also assayed 4 h after drug administration on days 1, 5, 10 and 12 and then again 12 and 24 h after the last dose of MSF given on day 12, the last dose in the multiple dose phase.
Subjects who dropped out for other than AEs were replaced and the replacements underwent both the single and multiple dose phases.
In a single-and multiple-dose phase I clinical trial in healthy Korean subjects.
