(1-Hydroxyethylidene)-1,1-diphosphonic acid

206.02800

206.03

220-552-8

M2F465ROXU

227995

DTXSID6023028

C1332

M - Musculo-skeletal system

2931900090

154.91000

-3.7

Liquid

1.45 (60% aq.)

155 °C (decomp)

578.8ºC at 760 mmHg

303.8ºC

1.586

Soluble in water.

8.34E-16mmHg at 25°C

LD50 oral in mouse: 1800mg/kg

II

8

UN 3265

2

R37/38; R41

S26-S39

SZ8562100

Xi

Stable. Incompatible with strong oxidizing agents.

P280-P305 + P351 + P338

H290-H318

THE SYSTEMIC TOXICITY, SKIN TOLERANCE & ECOTOXICITY OF PRIMARY MATERIALS USED IN THE TREATMENT OF WATER, EG, ANTICORROSION PHOSPHONATES WAS STUDIED. HYDROXYETHANE DIPHOSPHONIC ACID HAD LOW TOXICITY & PRESENTED NO POTENTIAL HAZARD.[KASTNER W ET AL; TOXICITY AND ECOTOXICITY OF WATER TREATMENT PRODUCTS; L' EAU, L' INDUSTRIE, LES NUISANCES 72: 47 (1983)]

|Danger|H290 (28.12%): May be corrosive to metals [Warning Corrosive to Metals]|P234, P260, P264, P270, P273, P280, P301+P312, P301+P330+P331, P303+P361+P353, P304+P340, P305+P351+P338, P310, P321, P330, P363, P390, P404, P405, and P501|Aggregated GHS information provided by 2240 companies from 32 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.|H302: Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P280, P301+P312, P305+P351+P338, P310, P330, and P501|P260, P264, P270, P280, P301+P312, P301+P330+P331, P303+P361+P353, P304+P340, P305+P351+P338, P309+P311, P310, P321, P330, P363, P405, and P501

Patients experiencing an overdose may present with hypocalcemia, vomiting, parasthesia, and diarrhea. Overdose can be treated with symptomatic and supportive treatment that may include management of electrolyte imbalances and intravenous calcium gluconate.

Etidronate is indicated to treat Paget's disease of bone, as well as the treatment and prevention of heterotropic ossification after total hip replacement of spinal cord injury.|FDA Label

Chelating Agents|EXPTL USE: 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID, DICHLOROMETHANEDIPHOSPHONIC ACID OR THEIR SALTS OR ESTERS REDUCED THE INCIDENCE OF TUMOR CELL METASTASIS IN BONE IN HUMANS.|BONE SCANNING AGENT WHEN LABELED WITH (99M)TECHNETIUM|CHELATING AGENT; CALCIUM REGULATING AGENT IN HUMAN MEDICINE|MEDICATION (VET): 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID, DICHLOROMETHANEDIPHOSPHONIC ACID OR THEIR SALTS OR ESTERS REDUCED THE INCIDENCE OF TUMOR CELL METASTASIS IN BONE IN ANIMALS.

Etidronic acid is a first generation bisphosphonate that inhibits the action of osteoclasts, preventing bone resporption. It has a wide therapeutic index as overdoses are not associated with severe toxicity and a long duration of action as it slowly releases from the bone. Patients should be counselled regarding the risk of upper gastrointestinal adverse reactions.

Agents that inhibit BONE RESORPTION and/or favor BONE MINERALIZATION and BONE REGENERATION. They are used to heal BONE FRACTURES and to treat METABOLIC BONE DISEASES such as OSTEOPOROSIS. (See all compounds classified as Bone Density Conservation Agents.)

Etidronic acid has an oral bioavailability of 1-10%. Further data regarding pharmacokinetics of etidronic acid are not readily available.|Absorbed etidronic acid is eliminated in the urine, while the unabsorbed drug is eliminated in the feces.|Etidronic acid has a volume of distribution of 0.3-1.3L/kg.|Etidronic acid has a renal clearance of 0.09L/kg/h.|THE DISTRIBUTION OF TECHNETIUM-99M HEDP IN NORMAL HUMAN ORGANS WAS MEASURED.|THE BONE-SEEKING AGENT (99M)TC-SN-1-HYDROXYETHYLIDENE-1,1-DIPHOSPHONIC ACID UNEXPECTEDLY BINDS TO PARTICLES OF HUMAN ARTICULAR CARTILAGE AS WELL AS CORTICAL BONE IN VITRO. MECHANISMS ADDITIONAL TO THE SIMPLE IONIC ATTRACTION BETWEEN THE PHOSPHONATE GROUPS OF HEDP & METAL CATIONS SUCH AS CA2+ ARE RESPONSIBLE FOR THE UPTAKE OF (99M)TC-HEDP BY BODY TISSUES.|THE AFFINITY CONSTANT WHICH CHARACTERIZES THE BINDING OF (99)TC-HYDROXYETHYLENE DIPHOSPHONATE (TC-HEDP) WITH HUMAN SERUM ALBUMIN WAS 7.8X10+4. A SINGLE SLOPE WAS OBTAINED.

Etidronic acid is not metabolized _in vivo_

The half life of etidronate is approximately 1-6 hours.

Bisphosphonates are taken into the bone where they bind to hydroxyapatite. Bone resorption by osteoclasts causes local acidification, releasing the bisphosphonate, which is taken into the osteoclast by fluid-phase endocytosis. Endocytic vesicles become acidified, releasing bisphosphonates into the cytosol of osteoclasts where they act. Osteoclasts mediate resorption of bone. When osteoclasts bind to bone they form podosomes, ring structures of F-actin. Disruption of the podosomes causes osteoclasts to detach from bones, preventing bone resorption. First generation bisphosphonates closely mimic the structure of pyrophosphate, which can be incorporated into ATP anologues that cannot be hydrolyzed, disrupting all ATP mediated actions of osteoclasts.|MALE RATS WERE INJECTED WITH VEHICLE (CONTROL GROUP), 0.4 OR 4.0 MG/KG/DAY OF ETHANE-1-HYDROXY-1,1-DIPHOSPHONATE (EHDP). AFTER 6 DAYS OF EHDP TREATMENT ALL RATS RECEIVED 6 SC INJECTIONS OF (3)H-THYMIDINE AT 8 HR INTERVALS. AFTER 6 DAYS OF EHDP PRE-TREATMENT THE MULTIPLE LABELING INDEX OF OSTEOPROGENITOR CELLS WAS REDUCED WITH 4.0 MG/KG/DAY DOSE OF EHDP. EHDP CAUSED INCR IN RATE OF INCORP & ACCUM OF (3)H-THYMIDINE NUCLEI IN OSTEOCLASTS. EHDP CAUSES AN ACCELERATED RATE OF OSTEOCLAST PRODN FROM PRECURSOR CELLS IN SPITE OF ITS ABILITY TO SLOW BONE RESORPTION.

IV ADMIN OF 5 MG 1-HYDROXYETHYLIDENE DIPHOSPHONATE (HEDP) DAILY TO YOUNG MALES FOR 5 DAYS DID NOT ALTER THE BLOOD & URINARY LEVELS OF CALCIUM & PHOSPHATE, & OTHER BIOCHEMICAL PARAMETERS.

(1-hydroxyethylene)diphosphonic acid

All other basic inorganic chemical manufacturing|Phosphonic acid, P,P'-(1-hydroxyethylidene)bis-: ACTIVE|WAVE-SETTING HAIR PREPARATIONS ARE PREPARED BY COMBINING L-CYSTEINE WITH 1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID. THE CHELATING AGENT PREVENTS FORMATION OF DANDRUFF.|CORROSION SCALE PREVENTION IN COOLING WATER TREATMENT BY ORGANOPHOSPHATES.|1-HYDROXYETHANE-1,1-DIPHOSPHONIC ACID IS USED IN HAIRSETTING PREPARATIONS. THE CHELATING AGENT PREVENTS FORMATION OF DANDRUFF.|1-HYDROXYETHYLDIPHOSPHONATE INCREASED BOVINE TOOTH ENAMEL ION-SELECTIVITY; THE EFFECT WAS RELATED TO THE NUMBER OF PHOSPHATE GROUPS & WAS GREATER WITH THE ORGANIC THAN INORGANIC PHOSPHATES.

PERTECHNETATE ION, A COMMON IMPURITY IN TECHNETIUM PHARMACEUTICALS, IS USUALLY DETERMINED BY PAPER OR THIN-LAYER CHROMATOGRAPHY. A HIGH PRESSURE LIQ CHROMATOGRAPHIC METHOD WAS DEVELOPED & COMPARED WITH PREVIOUS METHODS.|AN ANION-EXCHANGE HIGH-PERFORMANCE LIQ CHROMATOGRAPHIC SEPARATION OF TECHNETIUM HYDROXYETHYLIDENE DIPHOSPHONATE COMPLEXES WAS DEVELOPED. THREE MODES OF DETECTION WERE USED: (1) SINGLE WAVELENGTH AT 405 NM, (2) UV-VISIBLE RAPID SCANNING FROM 250-600 NM, & (3) SINGLE CHANNEL RADIOMETRIC SCINTILLATION. CHROMATOGRAMS ILLUSTRATE THAT THESE RADIOPHARMACEUTICAL ANALOGS CONSIST OF THE MIXTURES OF AT LEAST 7 TECHNETIUM-CONTAINING SPECIES OF UNKNOWN OXIDN STATE, CENTRAL METAL CONFIGURATION, & COORDINATION ENVIRONMENT.

ETHANE-1-HYDROXY-1,1-DIPHOSPHONATE, USED IN ORAL COMPOSITIONS SUCH AS TOOTHPASTE & MOUTHWASH, WAS EXCRETED IN HUMAN FECES & URINE & DETERMINED BY A COMPLEXOMETRIC SPECTROTITRATION PROCEDURE.|TECHNIQUE HAS BEEN DEVELOPED TO MEASURE ETHANE-1-HYDROXY-1,1-DIPHOSPHONATE (EHDP) QUANTITATIVELY IN 5 ML OF URINE OR 2 ML OF PLASMA. THE PROCEDURE IS BASED ON CO-PRECIPITATION OF EHDP WITH CALCIUM PHOSPHATE, ELIMINATION OF INORGANIC PHOSPHATE AS AN INSOL TRIETHYLAMINE-PHOSPHOMOLYBDATE COMPLEX, DECOMP OF P-C-P BOND WITH UV LIGHT & SPECTROPHOTOMETRIC DETERMINATION OF P-C-P BONE WITH UV LIGHT & SPECTROPHOTOMETRIC DETERMINATION OF THE INORGANIC PHOSPHATE RELEASED. THE LIMIT OF DETECTION IS IN THE ORDER OF 2.5 MUMOLE/L IN 5 ML URINE & 0.5 MUMOLE/L IN 2 ML OF PLASMA.

EPA Safer Chemical Functional Use Classes -> Oxidants and Oxidant Stabilizers|Safer Chemical Classes -> Yellow triangle - The chemical has met Safer Choice Criteria for its functional ingredient-class, but has some hazard profile issues|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients|Cosmetics -> Chelating