What Is Pamidronate?

Pamidronic acid is an anti-tumor drug with the trade names Bonin and Leanxin. This product can effectively inhibit osteoclast activity and inhibit osteoclast precursor maturation. The use of this product can reduce the amount of analgesic medicine.

Drug Name: Pamidronic acid

Foreign name: Pamidronic acid
Drug type: Antitumor

Pamidronate Basic Information

Chinese name: pamidronic acid

Chinese alias: (3-amino-1-hydroxypropylene) bisphosphonic acid; 3-amino-1-hydroxy-1,1-propane diphosphonic acid

English name: Pamidronic acid

English alias: Pamidronic Acid; Pamidronic Acid See P172500

CAS number: 40391-99-9

Molecular formula: C ₃ H ₁₁ NO ₇ P ₂

Molecular weight: 235.06900

Exact mass: 235.00100

PSA: 180.93000 ^[1]

Physicochemical properties of pamidronate

Appearance and properties: white crystalline powder

Density: 1.998 g / cm ³

Melting point: 226-228ºC

Boiling point: 658.7ºC at 760 mmHg

Flash point: 352.2ºC

Refractive index: 1.611

Pamidronate molecular structure data

1. Molar refractive index: 40.87

2. Molar volume (cm3 / mol): 117.6

3. Isometric Zhang Rong (90.2K): 403.5

4. Surface tension (dyne / cm): 138.5

5. Polarizability (10-24cm3): 16.20 ^[2]

Production method and application of pamidronic acid

production method

The aqueous solution of chlorobenzene and -aminopropionic acid was heated to about 100 ° C., phosphorus trichloride was added dropwise with stirring, and the reaction was then kept warm. Cool to room temperature. The hydrogen chloride gas was removed by passing nitrogen gas. The chlorobenzene solution was separated, and water was slowly added dropwise. The temperature was raised to 100 ° C. with stirring to react. Freeze crystallization and filtration to obtain pamidronic acid.

use

A potent osteoclastic bone resorption inhibitor. Pa ^[3] , idiopathic osteoporosis. The effect is significant and the side effects are low.

Pamidronate Related Pamphlet Information

Pamidronic acid

Drug Name

Common name: Pamidronate disodium for injection

[Ingredients]

Chemical name: 3-amino-1-hydroxypropylene-1,1-diphosphonic acid disodium pentahydrate

Molecular formula: C3H9NNa2O7P2 · 5H2O

Molecular weight: 369.11

[Indications]

Bone pain caused by malignant tumors with hypercalcemia and osteolytic cancer metastasis.

specification

(1) 15 mg; (2) 30 mg; (3) 60 mg.

Dosage

Treatment of bone metastatic pain: Dilute in calcium-free 0.9% saline or 5% glucose solution immediately before use. Intravenous slow drip for more than 4 hours, the concentration should not exceed 15mg / 125ml, and the drip rate should not exceed 15-30mg / 2 hours. 30-60mg in one dose.

Treatment of hypercalcemia: Medication should be used in strict accordance with the blood calcium concentration under the guidance of a doctor. General Recommended Dose:

Serum calcium concentration before treatment	Total calcium = free calcium + protein-bound calcium	Recommended total dose
(Mmol / l)	(Mg%)	(Mg)
<3.0	<12.0	15-30
3.0-3.5	12.0-14.0	30-60
3.5-4.0	14.0-16.0	60-90
> 4.0	> 16.0	90

This dosage guideline is based on uncorrected serum calcium values. Accurate standards should be determined based on serum protein corrected calcium values (ionized calcium).

Experience with this dose is limited.

Adverse reactions

Adverse effects with pamidronate disodium are usually mild and temporary. The most common adverse reactions were asymptomatic calcium, "flu-like" symptoms and mild fever (temperature rise> 1 ° C, which can last for 48 hours). Fever usually goes away without treatment. Acute "influenza-like" reactions usually only occur when first treated with pamidronate disodium. Symptomatic hypocalcemia is uncommon. A small number of patients may have mild nausea, chest pain, chest tightness, dizziness, fatigue, and slight changes in liver and kidney function. When using the highest dose for treatment, local soft tissue inflammation at the infusion site also occasionally occurs.

[Taboo]

Allergies to pamidronate disodium or other bisphosphonate preparations are contraindicated.

Precautions

This product should be slowly infused intravenously immediately after dilution with a calcium-free liquid. Do not directly inject this product intravenously.

This product should not be used in combination with other types of bisphosphonates.

This product is mainly excreted by the kidney, so the risk of renal adverse reactions in patients with renal insufficiency is correspondingly increased. Therefore, patients who frequently receive this infusion for a long time, especially those with concurrent kidney and disease or increased sensitivity to renal impairment (such as patients with multiple myeloma and / or tumor-induced hypercalcemia) should be regularly evaluated. Its laboratory and clinical data on renal function.

Because there is no clinical trial data on the use of this product in patients with severe liver function impairment, it is not currently possible to recommend such patients.

When used for the treatment of hypercalcemia, pay attention to supplement fluid at the same time, so that the daily urine output reaches more than 2L.

During the use of this product, care should be taken to monitor serum calcium, phosphorus and other electrolyte levels.

[Medication for pregnant and lactating women]

Pregnant women should weigh the advantages and disadvantages of medication, the drug can enter the breast milk, so use it with caution when breastfeeding.

[Medicine for the elderly]

Appropriate reduction.

medicine interactions

1. The combined application of this product and calcitonin in patients with severe hypercalcemia can produce a synergistic effect, resulting in a more rapid decrease in serum calcium.

2. Pay attention to this product and other potentially nephrotoxic drugs. When this product is combined with oligodamine to treat multiple myeloma, the risk of worsening renal function is increased.

Other interactions have not been studied.

[Drug overdose]

Excessive or too fast, may cause hypocalcemia, twitching, numbness of fingers, and appropriate calcium supplementation.

[Pharmacological action]

This product is a bisphosphonate drug. In vitro and animal tests show that it can strongly inhibit the dissolution of hydroxyapatite and the activity of osteoclasts, and it has a very significant inhibitory effect on bone absorption. It has analgesic effect on pain caused by osteolytic bone metastasis of cancer, and can also be used to treat hypercalcemia caused by cancer.

Pharmacokinetics

It is reported in the literature that cancer patients take 45mg of this product dissolved in 500ml of normal saline for more than 4 hours after intravenous infusion. At the end of the infusion, the blood concentration is 0.96g / ml, and an average of 51% of the drug is excreted from the urine in the original form. The kinetic characteristics of biphasic treatment are shown. The alpha and beta half-life are 1.6 hours and 27.2 hours, respectively. Animal experiments show that it is rapidly eliminated from the circulatory system after administration and is mainly distributed in bones, liver, spleen and tracheal cartilage. This product can stay in the bone tissue for a long time, and the half-life can be up to 300 days.

Liver damage

In a pharmacokinetic study of male cancer patients with bone metastases with normal liver function (n = 6) and mild to moderate liver damage (n = 9), each patient was given a single dose of 90 mg of this product and instilled 4 For more than hours, the average AUC (39.7%) and Cmax (28.6%) of patients with liver damage showed higher values than those with normal liver function, but no matter how the liver damage was, the plasma clearance of pamidronate was rapid. After hours, no active substance was detected in the blood. Since the course of administration of this product is one month, no drug accumulation will occur, so patients with mild to moderate liver damage do not need to adjust the dosage.

Kidney damage

Pharmacokinetic studies of cancer patients showed that there was no difference in the area under the curve (AUC) of pamidronate in plasma between patients with normal renal function and patients with mild to moderate renal impairment. Patients with severe renal impairment (creatinine clearance <30 ml / min) had an average plasma area under the curve (AUC) approximately three times that of normal patients (creatinine clearance> 90 ml / min).

Storage

Shaded, sealed and stored in a cool place.

package

Xilin bottle, 1 bottle / box.

[Validity Period]

24 months.