Pharmacokinetics and Tolerability of Minodronic Acid and Food and Age Effects on the Pharmacokinetics

This was a single-center, phase I study in healthy young (19-30 years) and elderly (60-65 years) volunteers, which was conducted in four parts. In Part 1, minodronic acid tablets were administered to young volunteers at doses of 1, 2, and 4 mg. In Part 2, after a single dose, young volunteers in the 1-mg dose group received repeated oral doses of minodronic acid once daily for 7 days. In Part 3, a single oral dose of minodronic acid 1 mg was administered to elderly volunteers. In part 4, after a washout period of 8 days, volunteers in the 4-mg dose group received a single dose of 4 mg minodronic acid under fed conditions (administrated 30 minutes before high-fat breakfast). Plasma samples were collected and plasma concentrations of minodronic acid were analyzed by LC-MS/MS. Tolerability was assessed throughout the study by physical examinations, vital signs measurement, laboratory analyses, and monitoring of adverse effects.

Inclusion criteria

• Subjects were included based on the following criteria:

• males or females aged 19 to 35 years for young subjects or aged 60 to 65 years for elderly subjects
• body mass index between 19 and 24 kg/m2
• thorax radiography and ECG with no abnormalities
• normal blood pressure values
• heart rate
• laboratory test results (hematology, blood biochemistry, hepatic function, and urinalysis)
• negative test results for HIV and hepatitis B.

Exclusion criteria

• Subjects were excluded if they had a heart disease or disorder
• A hepatic, renal, respiratory, immune system, or nervous system disorder
• Any of the following conditions:

• pregnancy
• breast-feeding
• hypocalcemia
• prescription or over-the-counter medication use (including herbal products) within 2 weeks before the initiation of the study
• blood donation or participation in other clinical trials within 3 months before enrollment in the study
• alcohol or drug abuse
• smoking more than 10 a day
• clinically significant allergies to drugs or foods
• sitting blood pressure <80/50 mm Hg or >140/100 mm Hg
• A ventricular rate <60 beats/min or >100 beats/min at rest.