On Jan 8, 10:40 pm, ironjustice <teamtan...@hotmail.com> wrote:no
evidence currently available to definitely confirm that

"Osteoporosis, malignancies and rheumatoid arthritis"

Olpadronate: a new amino-bisphosphonate for the treatment of medical
osteopathies
Authors: Roldn E.J.A.1; Prez A.2; Roldn J.L.3

Source: Expert Opinion on Investigational Drugs, Volume 7, Number 9,
September 1998 , pp. 1521-1538(18)

Abstract:

Olpadronate is a nitrogenated bisphosphonate. Although it shares the
therapeutic and pharmacological properties of pamidronate and
alendronate, it has a greater dosage amplitude, more predictable
effects and a greater digestive tolerability than other bisphosphates.
Therefore, it may be more appropriate in the treatment of medical
osteopathies, by both oral and parenteral routes of administration.
According to various experimental and human models, the
pharmacological potency of olpadronate is 5- to 10-times higher than
that of pamidronate and close to that of alendronate. The two methyl
groups bound to the nitrogen atom give the compound a high water
solubility, which is about 8-times higher than that of the two other
bisphosphonates. The lack of a terminal amino group in the side-chain
of the molecule and the absence of crystallised forms of the compound
in the digestive tract (due to its high water solubility) may avoid
the potential for inducing oesophageal and gastrointestinal side-
effects. These features may explain the high tolerability reported
after the administration of doses of olpadronate (by the oral route)
up to 5- to 10-times higher than the maximum tolerated dose of
alendronate in Paget's bone disease and bone metastases, thus widening
the possibilities for its clinical usage. In addition, initial
pharmacokinetic studies suggest that olpadronate's oral
bioavailability would fit into a confidence range of 2 - 4%, which
contrasts with the erratic absorption shown by other highly potent
bisphosphonates. The clinical efficacy demonstrated in preliminary
studies in Paget's bone disease (including ultra-short treatments),
and also in single-dose iv. therapy of hypercalcaemia of malignancies,
renders olpadronate among the most promising bisphosphonate compounds,
with potential use in the treatment of a variety of bone-involving
diseases, such as osteoporosis, malignancies and rheumatoid arthritis.

Keywords: bisphosphates; bone metastasis; bone strength;
hypercalcemia; olpadronate; osteoporosis; Paget's bone disease

Document Type: Miscellaneous

Affiliations: 1: Department of Clinical Pharmacology, Gador SA, Buenos
Aires 2: Department of Clinical Pharmacology, Gador SA, Buenos Aires
3: Center for Metabolic Studies on Calcium and Phosphorus (CEMFOC),
National University of Rosario, Rosario, Argentina

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