Phase I Study of Alendronate, a New Aminobisphosphonate

Phase I studies of MK-217, a new aminobisphosphonate, were conducted in 27healthy Japanese male volunteers. The safety, tolerability and pharmacokinetics wereinvestigated. In a single-dose study, 5, 10, 20 and 40 mg of MK-217 were administered to12 subjects. In a 7-day multiple dose study, 20 mg was administered to 6 subjects. Inaddition, either 20 mg or placebo were administered to 9 subjects (20 mg: 6, placebo: 3) in a 14-day multiple-dose study which was a double-blinded, placebo controlled study.No abnormal changes were observed in subjective symptoms, blood pressure, pulserate, respiratory rate, body temperature and ECG in each study. An increase in GPT wasobserved in one subject after a single dose of 5 mg.In the 7-day multiple-dose study, elevations in GOT, GPT, Al-p andγ-GTP wereobserved in one subject who had flu-like symptoms. GPT and Al-p were increased inanother subject in this study. In the 14-day multiple dose study, however, there were noabnormal changes.In the single-dose study, the serum concentration of MK-217 was under the detectable limit after 5 mg and 10 mg administration. In all three studies less than 2% ofadministered doses were excreted in urine.