Absorption of Oral Diphosphonate in Normal Subjects

Fogelman, Ignac; Smith, Lorraine; Mazess, R.B.; Ma, Wilson; Ja, Bevan

doi:10.1111/j.1365-2265.1986.tb03254.x

Cited by 112 publications

(28 citation statements)

References 11 publications

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“…Using radiolabelled pamidronate it is estimated that, in rats, 2% of the oral dose is absorbed (Ciba-Geigy, data on file). Estimates of the absorption of another bisphosphonate (etidronate) range from 1 to 9% (Fogelman et al, 1986). The effect of oral bisphosphonates on calcium release from bone may however be assayed indirectly by estimating their effect on the urinary Ca2+/Cr ratio.…”

Section: Discussionmentioning

confidence: 99%

Reduction in calcium excretion in women with breast cancer and bone metastases using the oral bisphosphonate pamidronate

Howell¹,

Ford²

1990

Br J Cancer

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Summary The bisphosphonate pamidronate (3 amino-I, 1-hydroxypropylidene bisphosphonate (APD), CibaGeigy) is a powerful inhibitor of osteoclast function and has been shown to significantly reduce osteolysis associated with bone metastases in breast cancer. Until recently, however, only an intravenous preparation has been readily available. We have evaluated the toxicity and effect on urinary calcium excretion of an enteric-coated oral preparation of pamidronate in a phase I/II trial in patients with bone metastases from breast cancer. Sixteen women with progressive disease and evidence of active bone resorption with an elevated calcium excretion (fasting urine calcium/creatinine ratio >0.4 (mmol mmol-') on two occasions prior to treatment) were studied. Four were given 150 mg daily; four 300 mg daily; four 450 mg daily and four 600 mg daily. Urinary calcium/creatinine (Ca2+/Cr) ratios were measured on all patients after an overnight fast. In patients on 150mg daily the mean ratio fell from 0.65 (range 0.57-0.72) before treatment to 0.13 (0.02-0.19) after three weeks treatment. Mean values at entry for patients on 300, 450 and 600 mg were 1.18 (0.72 -2.1), 0.76 (0.42-1.5) and 0.63 (0.52-0.82) respectively and after treatment these fell to 0.11 (0.05-0.18), 0.37 (0.14-0.68) and 0.17 (0.06-0.25). There were no significant differences in efficacy between treatment groups. Oral, enteric-coated disodium pamidronate is non-toxic and effectively reduces calcium excretion, raised in association with metastatic bone disease at doses of 150mg or above. At the doses used to date it is as effective as weekly treatments with 30 mg of the intravenous preparation. Further studies are required in order to determine its value for preventing complications of bone disease and possibly as an adjuvant to surgery for breast cancer.The bisphosphonates are a class of compounds which are enzyme resistant analogues of pyrophosphate, the naturally occurring inhibitor of bone mineralisation. They are known to bind to hydroxyapatite crystals, cause inhibition of osteoclast function and slow the rate of osteoclast mediated bone resorption (Fleish, 1983). They are the treatment of choice for the hypercalcaemia of malignancy, a syndrome characterised, almost invariably, by excessive bone resorption and, when used in combination with fluid replacement, are over 90% effective in restoring normocalcaemia (Morton et al., 1988a; Jung et al., 1981). One early, placebo-controlled study (van Holten-Verzantvoort et al., 1987) using a locally manufactered oral APD preparation in combination with standard treatment was encouraging, with a reduced incidence of pathological fracture, hypercalcaemia and requirement for radiotherapy at the sites of painful bone lesions in the treated group. However, 8% of patients stopped taking the drug because of gastrointestinal toxicity.Recently there have been reports of the benefits of therapy with intravenous pamidronate alone in patients with metastatic bone disease (Morton et al., 1988b;Coleman et al., 1988). They in...

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Section: Discussionmentioning

confidence: 99%

Reduction in calcium excretion in women with breast cancer and bone metastases using the oral bisphosphonate pamidronate

Howell¹,

Ford²

1990

Br J Cancer

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“…The intestinal absorption of etidronate has been shown to be approximately 3% in the fasting state. 26 The administration ofa single dose of 0.04 mmol of etidronate per body weight (kg) 30 minutes before breakfast to healthy subjects revealed that only 1.04% of the total dose was excreted within 24 hours.4 When 200 mg of etidronate is given, the total excretion in the urine may be at least 8 pmol for 24 hours. It is not clear whether the effect ofpreventing stone recurrence can be achieved under these conditions.…”

Section: Effect Of Etidronate On the Adhesion Of Calcium Oxalate Crysmentioning

confidence: 99%

Effects of Etidronate Disodium on Crystallizations in Synthetic Urine and Calcium Oxalate Crystal Adhesion to Madin‐Darby Canine Kidney (MDCK) Cells

et al. 1998

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Background: Several reports in the 1970s suggested that etidronate disodiurn might be clinically useful to prevent calcium stones, but the use of etidronate in the urolithiasis field was discontinued due to adverse effects of this drug on skeletal turnover and mineralization. Because the drug might affect not only crystallization, but also crystal-tubular interactions, we investigated the minimum dose of etidronate necessary to effectively prevent stone recurrence without adverse side effects. Methods: We examined the effect of etidronate on the crystallization of calcium oxalate, calcium phosphate and magnesium ammonium phosphate using synthetic urine and measured by an aggregometer. Wealsostudied itseffect on theadhesion ofcalciumoxalate monohydratecrystals toMadin-Darbycanine kidney (MDCK) cells in vitro. Results: Etidronateaffected thecrystallization of notonlycalcium phosphateand calcium oxalate, butalso magnesium ammonium phosphate in synthetic urine. The inhibitory activities on these crystallizations were detected at extremely low drug concentrations. Etidronate also had a strong inhibitory activity against the adhesion of calcium oxalate crystals to MDCti cells. Conclusion:Although further studies are necessary regarding the effects of etidronate on crystallization and crystal adhesion both in vivo and in vitro, and the appropriate schedule of dosing to prevent side effects, it is possible that etidronate may be useful in the treatment of urinary stones.Int J Urol 1998;5:582-587

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“…Bisphosphonates are poorly absorbed from the gastrointestinal tract (25)(26). In the case of clodronate, absorption lies between 1-6% of the administered dose (27)(28).…”

Section: Mechanism Of Action Of Bisphosphonatesmentioning

confidence: 99%

Clodronate and Other Bisphosphonates as Supportive Therapy in Osteolysis Due to Malignancy

Elomaa¹,

Blomqvist²

1995

Acta Oncologica

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Absorption of Oral Diphosphonate in Normal Subjects

Cited by 112 publications

References 11 publications

Reduction in calcium excretion in women with breast cancer and bone metastases using the oral bisphosphonate pamidronate

Reduction in calcium excretion in women with breast cancer and bone metastases using the oral bisphosphonate pamidronate

Effects of Etidronate Disodium on Crystallizations in Synthetic Urine and Calcium Oxalate Crystal Adhesion to Madin‐Darby Canine Kidney (MDCK) Cells

Clodronate and Other Bisphosphonates as Supportive Therapy in Osteolysis Due to Malignancy

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