Preliminary study of multiple increasing oral doses of dimethyl-APD on bone metabolism dynamics and safety profile.

A random block study, with 50, 100, 200 and 400 mg of 3-dimethylamino-1-hydroxypropylidene-1, 1-bisphosphonate or dimethyl APD and 300, 600 and 900 mg of 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate or pamidronate (APD), in daily oral doses, showed that all doses were active when assessed in patients with Paget's bone disease. Dimethyl APD administration was followed by an increase in 1.25 (HO)2D levels, an effect that must be confirmed. Neither severe side effects nor significant laboratory abnormalities were detected despite some decrease in white blood cell count seen with the higher dose of APD. Gastrointestinal tolerance of dimethyl APD was acceptable but further investigation is required.