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Blocking of bone resorption by osteoclasts tissue in vivo may be incomplete, and as a minimum, is the result of binding of the drug to the bone minerals. Pamidronic acid inhibits osteoclast precursors migrate into the bone tissue, disrupting their maturation. However, the local and direct antiresorptive effect of bisphosphonates due affinity for the mineral components of bone is the predominant mechanism of action in vivo and in vitro . Biochemical changes characterizing the inhibitory effect pamidronic acid on tumor-induced buy testosterone enanthate hypercalcemia manifest reduction of calcium indicators, phosphates and second, lower excretion of calcium, phosphate and hydroxyproline excretion. The dose of 90 mg in normocalcaemia provides more than 90% of patients.

Hypercalcemia may reduce the volume of extracellular fluid, and reduction of glomerular filtration capacity. By controlling hypercalcaemia, pamidronic acid improves glomerular filtration and reduces elevated creatinine in most patients. In patients with bone metastases (predominantly osteolytic nature) of malignant tumors and multiple myeloma drug prevents or slows the progression of skeletal changes and their consequences (hypercalcemia, fractures, need for radiation therapy and surgery, spinal cord compression) and also reduces pain in the bones.
Pamidronic acid has a pronounced tropism towards calcified tissues, which are considered “a place of apparent elimination” pamidronic acid.
Pamidronic acid concentration in plasma increases rapidly immediately after the start of infusion and decreases rapidly after its completion. The half-life from the blood plasma is about 0.8 hours. The equilibrium concentration is achieved for more than 2-3 hours. With intravenous infusion of 60 mg of more than 1 hour, the maximum concentration of pamidronic acid in plasma (C max ) is about 10 nmol / ml.
A similar percentage (about 50%) pamidronic acid distributed in the body after administration of different doses (30-90 mg) regardless of the duration of infusion (4 or 24 hours). Thus, accumulation in bone pamidronic acid quantitatively unlimited and depends solely on the total cumulative dose. Number of circulating pamidronic acid bound to plasma proteins is relatively low (less than 50%) and can be increased with the pathological increase in calcium buy testosterone nanthate concentration.
It is believed that the acid is not pamidronic biotransformation and excreted almost exclusively by the kidneys.

After intravenous administration, approximately 20-55% of the injected dose detected in the urine within 72 hours as unchanged. The residual fraction of the administered dose can be detected in the body.Pamidronic acid excretion in urine dwuhfazno, apparent half-lives are, respectively, 1.6 and 27 hours. The total plasma and renal clearance is 88254 ml / min and 38-60 ml / minute, respectively. The average plasma clearance is about 180 ml / minute. The average renal clearance – 54 ml / minute. Renal clearance pamidronic acid correlates with creatinine clearance.
Hepatic and metabolic clearance pamidronic acid is negligible. In this regard, liver dysfunction not affect the pharmacokinetics of pamidronate disodium.
Differences between pamidronic acid content in plasma of patients with normal renal function in patients with mild or moderate renal impairment exists. In patients with severe renal impairment (creatinine clearance of 30 ml / minute) pamidronate content was about three times higher than in patients with normal renal function (creatinine clearance of> 90 ml / minute).

Indications
Diseases accompanied by increased osteoclast activity:

  • bone metastases of malignant tumors (predominantly osteolytic nature) and multiple myeloma (multiple myeloma);
  • hypercalcemia due to malignancy.

Contraindications

  • Hypersensitivity to pamidronic acid or other bisphosphonates, as well as to the other ingredients included in the formulation.
  • Pregnancy and lactation.
  • Children’s age (experience buy testosterone enanthate in the application of missing children)

Precautions: renal impairment.

Dosage and administration
intravenously by infusion. The infusion rate should not exceed 60 mg / hour (1 mg / min). Avoid extravasation. Use in adults and elderly patients with bone metastases of malignant tumors (predominantly osteolytic nature), and multiple myeloma. The recommended dose of pamidronate Medak is 90 mg every 4 weeks. This dose may also be administered with a 3-week interval, if there is the need to synchronize with chemotherapy. When bone metastases of malignant tumors of the drug is administered as a 2-hour infusion. When osteolytic bone lesions in multiple myeloma drug is introduced into 500 ml of solution in a 4-hour infusion. Hypercalcemia due to malignancy . Before starting the application, or pamidronate Medak during therapy is recommended to the patient rehydration using 0.9% sodium chloride solution. The total dose of pamidronate Medak exchange rate depends on the initial level of calcium in the blood serum of the patient. The following recommendations are designed to neskorregirovannyh values buy testosterone enanthate of calcium concentration in the serum.