Zoledronate was introduced in Canada as a lyophilized powder in vials for infusion as
solution in the treatment of tumor-induced hypercalcemia. This third-generation
bisphosphonate can be obtained by reaction of 2-(1-imidazolyl)acetic acid hydrochloride
with phosphorous trichloride followed by hydrolysis in concentrated hydrochloric acid,
Zoledronate originated from a medicinal chemistry program started at Novartis,
Switzerland in 1986 and aimed at discovering a follow-up to pamidronate for the treatment
of osteoporosis and metastatic bone disease. It has highly potent inhibitory effect on
hypercalcemia induced by vitamin Ds both in vitro in mouse calvarial cultures and in viva in
the thyroparathyroidectomized rat. It is respectively 100 and 850-fold more potent than
pamidronate in the former and latter tests. Clinically, it was demonstrated that zoledronate
achieved normalized serum calcium concentrations in a significantly higher percentage of
cancer patients compared to pamidronate. The 5 minute infusion with zoledronate was
more convenient than the 2 hour infusion necessary with pamidronate.
