Improved dosage form of the combined alendronate and calcitriol (Maxmarvil^®) on the absorption of alendronate in Korean postmenopausal women

Abstract

Alendronate is one of the most potent anti-osteoporotic agents for postmenopausal osteoporosis. However, high doses of alendronate cause esophageal irritation, myalgia, gastrointestinal discomfort and decrease of serum calcium level. Recently, Maxmarvil^® was developed as an enteric-coated tablet containing alendronate (5 mg) and calcitriol (0.5 μg) to minimize these side effects of alendronate. In the present study, we evaluated the pharmacokinetic profile and examined the incidence of unfavorable effects after oral administration of Maxmarvil^® in Korean healthy postmenopausal women without a previous history of fracture. In the in vitro dissolution test, alendronate was not released from Maxmarvil^® in pH 1.2 phosphate buffer solution but released in pH 6.0 and 6.8 phosphate buffer solutions and completely dissolved in 30 min. After oral administration of Maxmarvil^®, three out of 18 (16.7 %) women showed mild adverse effects; two myalgia and one upper gastrointestinal discomfort without heartburn. Most of these complaints disappeared during the study without additional treatment. The peak (U _max) and the average (U _ave) urinary excretion rate of alendronate and the time to reach U _max (T _max) were 2.94 μg/h, 0.901 μg/h and 6.77 h, respectively. The total cumulative urinary excretion of alendronate (Ae_0–24 h) was 21.6 μg (0.432 % of oral alendornate), which was similar to the reported values. Taken together, enteric-coated Maxmarvil^® is less harmful for the esophagus and gastrointestinal mucosa, shows the same pharmacokinetic profile to conventional alendronate (70 mg) and improves the tolerability of medication in clinical practice.