Pamidronate

Bone Metabolism. Figure 3 Chemical structure of pyrophosphate (a) and the bisphosphonates etidronate (b), clodronate (c), pamidronate (d), ibandronate (e). alendronate (f), risedronate (g), zoledronate (h). 

C3H7NO2 107-95-9) see Balsalazide sodium Calcium pantothenate Pamidronic acid L-alanine benzyl ester... 

C1H9NO 156-87-6) see Acamprosate calcium Cyclophosphamide Dexpanthenol Domperidone Gusperimus trihydrochloride Mefenorex Urapidil 7-amino-3-[(Z)-l-propenyl]-3-cephem-4-carboxylic acid (CiqHi2N203S 106447-44-3) see ci s-Cefprozil 3-aminopropionaIdehyde diethyl acetal (C7H,7N02 41365-75-7) see Atorvastatin calcium P-aminopropionic acid phosphite (C3H, N0 P) see Pamidronic acid... 

There is considerable interest in using injectable bisphosphonates, such as pamidronate and zoledronic acid, in patients unable to tolerate or absorb oral bisphosphonates. Zoledronic acid in particular has a potential advantage of once-yearly dosing. Currently, neither drug has received FDA approval for this indication. Ibandronate has recently been approved for this indication. 

For women whose breast cancer has metastasized to bone, bisphosphonates are recommended, in addition to chemotherapy or endocrine therapy, to reduce bone pain and fractures.28,64 Pamidronate (90 mg) and zoledronate (4 mg) can be given intravenously once each month. These bisphosphonates are given in combination with calcium and vitamin D. 

Bone disease is a common manifestation of multiple myeloma. Bisphosphonates should be initiated in symptomatic patients with bone lesions to slow osteopenia and reduce the fracture risk associated with the disease. Pamidronate and zolendronic acid have equivalent efficacy in the management of osteolytic lesions, but because of relative ease of administration, zolendronic acid is used most frequently.43 The use of zolendronic acid decreases pain and bone-related complications and improves quality of life. The suggestion that bisphosphonates have direct antimyeloma activity, based on the ability to inhibit NF-kB signaling, remains controversial. Recent cases of osteonecrosis of the jaw have been a major concern. Risk factors are unclear, but osteonecrosis of the jaw is more common in patients receiving intravenous administration of bisphosphonates and having dental procedures performed. It is recommended that patients... 

Pamidronate and zoledronic acid are used most commonly and are potent inhibitors of osteoclast activity.29 The choice of bisphosphonate is a difficult one zoledronic acid is more efficacious in terms of response rate and longer duration of nor-mocalcemia but is approximately four times more expensive.30 Regardless of selection, the bisphosphonates should be administered at diagnosis owing to their delayed onset of action. 

Antiresorptive therapy Pamidronate 60-90 mg IV over 2-24 hours3 24-72 hours 3-4 weeks Greater than 1 mg/dL Nadir not seen until after 4-7 days may... 

Zoledronic acid 4 mg IV over 15 minutes 24-48 hours 4+ weeks Greater than 1 mg/dL cause fever, renal dysfunction pamidronate less expensive. 

In other studies, bisphosphonate-pamidronate or alendronate were linked to the terminal carboxylic acid of the stabilized dipeptide Pro-Phe to improve the bioavailability of bisphosphonates by hPepTl-mediated absorption. In-situ single-pass perfused rat intestine studies revealed competitive inhibition of transport by Pro-Phe, suggesting carrier-mediated transport. Oral administration of the dipeptidyl prodrugs resulted in a 3-fold increase in drug absorption following oral administration to rats. The authors suggested that oral bioavailability of bisphosphonates may be improved by PepTl-mediated absorption when administered as peptidyl prodrugs [53]. Future mechanistic studies may prove if hPepTl is involved in the absorption process. 

Pamidronate -organic bisphosphonate inhibits bone resorption by osteoclasts -hypotension -syncope -tachycardia -hypocalcemia, hypokalemia, hypomagnesemia -nausea and vomiting rarely... 

Bisphosphonates such as pamidronate and zoledronic acid may prevent skeletal morbidity, such as pathologic fractures and spinal code compression, when used for hormone-refractory prostate cancer in patients with clinically significant bone loss. Usual dosages are pamidronate, 90 mg every month, and zoledronic acid, 4 mg every 3 to 4 weeks. 

Pamidronate 30-90 mg IV over 2-24 hours 2 days Renal insufficiency Fever... 

Tubulointerstitial disease Acute allergic interstitial nephritis Pamidronate Nephrocalcinosis... 

The oral absorption of an entirely different class of drugs, namely bisphosphonates, has also been improved by a peptide prodrug strategy [36]. The drugs pamidronate (6.13, n=2) and alendronate (6.13, n=3) were deriv-atized with the Pro-Phe-dipeptidyl unit to yield the prodrugs Pro-Phe-pamidronate (6.14, n=2) and Pro-Phe-alendronate (6.14, n=3), the ob-... 

King LE, Vieth R. Extraction and measurement of pamidronate from bone samples using automated pre-column derivatization, high-performance liquid chromatography and fluorescence detection. J Chromatogr B 1996 678 325-330. 

The brand-name company admitted that Aredia was sold as the anhydrous (lacking water) form of pamidronate, not the pentahydrate form, which contains five water molecules for every pamidronate molecule. Ben Venue Labs., Inc. v. Novartis Pharm. Corp., 10 F. Supp. 2d 446, 454 (D. N.J. 1998) (the court did not address whether the generic applicant had a private right of action to challenge the listing). 

Bisphosphonates structurally mimic endogenous pyrophosphate, which inhibits precipitation and dissolution of bone minerals. They retard bone resorption by osteoclasts and, in part, also decrease bone mineralizatioa Indications include tumor osteolysis, hypercalcemia, and Paget s disease. Qinical trials with etidronate, administered as an intermittent regimen, have yielded favorable results in osteoporosis. With the newer drugs clodronate, pamidronate, and alendronate, inhibition of osteoclasts predominates a continuous regimen would thus appear to be feasible. 

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