프로카바진

MW: 257.77. Crystals from methanol, mp 223-226 °C. /Hydrochloride/

White to pale yellow crystalline powder ... soluble but unstable in water or aqueous solutions, mw = 257.76 /Hydrochloride/

Crystals from methanol and ether, decomposes at 216-217 °C /Hydrobromide/

White to pale yellow, crystalline powder; slight odor and bitter taste; 1 g sol in about 7 mL water, 100 mL alcohol, 10 mL methanol, 1000 mL acetone, ether, 1000 mL benzene, 1000 mL chloroform; solution are acid to litmus; pKa at room temp 6.8 /hydrochloride/

Hydroxyl radical reaction rate constant = 1.5X10-10 cu cm/molecule-sec @ 25 °C /Estimated/

SRP: The most favorable course of action is to use an alternative chemical product with less inherent propensity for occupational exposure or environmental contamination. Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in soil or water; effects on animal, aquatic, and plant life; and conformance with environmental and public health regulations.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All contaminated disposables should be contained in sealable bags for transfer to larger waste containers. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ All bottles must be discarded as contaminated waste after decontamination of the biohazard cabinet. All protective apparel (gown, gloves, goggles, and respirator) should be discarded as contaminated waste. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The contaminated filters must be removed, bagged in thick plastic and prepared for disposal in a hazardous waste dump site or incinerator licensed by the Environmental Protection Agency (EPA). /Antineoplastic agents/

For more Disposal Methods (Complete) data for PROCARBAZINE (8 total), please visit the HSDB record page.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Accidental contamination of the health-care environment, resulting in exposure of personnel, patients, visitors, and family members to hazardous substances, is prevented by maintaining the physical integrity and security of packages of hazardous drugs. 1. Access to all areas where hazardous drugs are stored is limited to specified authorized staff. 2. A method should be present for identifying to personnel those drugs that require special precautions (eg, cytotoxics). One way to accomplish this is to apply appropriate warning labels to all hazardous drug containers, shelves, and bins where the drug products are stored. ... 3. A method of identifying, for patients and family members, those drugs that require special precautions in the home should be in place. This may be accomplished in the health-care setting, by providing specific labeling for discharge medications, along with written instructions. 4. Methods for identifying shipping cartons of hazardous drugs should be required from manufacturers and distributors of these drugs. 5. Written procedures for handling damaged packages of hazardous drugs should be maintained. Personnel involved in shipping and receiving hazardous drugs should be trained in these procedures, including the proper use of protective garments and equipment. Damaged shipping cartons of hazardous drugs should be received and opened in an isolated area (eg, in a laboratory fume hood, if available, not in a vertical laminar airflow biological safety cabinet used for preparing sterile products). /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Facilities (eg, shelves, carts, counters, and trays) for storing hazardous drugs are designed to prevent breakage and to limit contamination in the event of leakage. Bins, shelves with barriers at the front, or other design features that reduce the chance of drug containers falling to the floor should be used. Hazardous drugs requiring refrigeration should be stored separately from nonhazardous drugs in individual bins designed to prevent breakage and to contain leakage. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Until the reproductive risks (or lack thereof) associated with handling hazardous drugs within a safety program have been substantiated, staff who are pregnant or breast-feeding should be allowed to avoid contact with these drugs. Policies should be in effect that provide these individuals with alternative tasks or responsibilities if they so desire. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ The pharmacy should provide access to information on toxicity, treatment of acute exposure (if available), chemical inactivators, solubility and stability of hazardous drugs (including investigational agents) used in the workplace. /Antineoplastic agents/

For more Preventive Measures (Complete) data for PROCARBAZINE (19 total), please visit the HSDB record page.

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Protective apparel: Disposable closed-front gown or coveralls, disposable utility gloves over disposable latex gloves, NIOSH-approved air-purifying half-mask respirator equipped with a high efficiency filter, and eye protection should be worn. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Class 100 clean-air work stations, both horizontal and vertical airflow (with no containment characteristics), are inappropriate engineering controls for handling hazardous drugs because they provide no personnel protection and permit environmental contamination. Although there are no engineering controls designed specifically for the safe handling of hazardous chemicals as sterile products, Class II contained vertical-flow biological safety cabinets (biohazard cabinets) have been adopted for this use. Biohazard cabinetry is, however, designed for the handling of infectious agents, not hazardous chemicals. ... Based on design, ease of use, and cost considerations, Class II contained-vertical-flow biohazard cabinetry is currently recommended for use in preparing sterile doses of hazardous drugs. Class II cabinetry design and performance specifications are defined in NSF Standard 49. Biological safety cabinets selected for use with hazardous drugs should meet NSF Standard 49 specifications to ensure the maximum protection from these engineering controls. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers should wear powder free, disposable surgical latex gloves of good quality when preparing hazardous drugs. Selection criteria for gloves should include thickness (especially at the fingertips where stress is the greatest), fit, length, and tactile sensation. ... The practice of double gloving is supported by research that indicates that many glove materials vary in drug permeability even within lots; therefore, double gloving is recommended. ... In general, surgical latex gloves fit better, have appropriate elasticity for double gloving and maintaining the integrity of the glove-gown interface, and have sufficient tactile sensation (even during double gloving) for stringent aseptic procedures. ... Powdered gloves should be avoided. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ Workers who are not protected by the containment environment of a biohazard cabinet should use respiratory protection when handling hazardous drugs. Respiratory protection should be an adjunct to and not a substitute for engineering controls. Surgical masks of all types provide no respiratory protection against powdered or liquid aerosols of hazardous drugs. In situations where workers may be exposed to potential eye contact with hazardous drugs, an appropriate plastic face shield or splash goggles should be worn. /Antineoplastic agents/

/PRECAUTIONS FOR ANTINEOPLASTIC AGENTS:/ During compounding of hazardous drugs (eg, crushing, dissolving, and preparing an ointment), workers should wear low permeability gowns and double gloves. Compounding should take place in a protective area such as a disposable glove box. If compounding must be done in the open, an area away from drafts and traffic must be selected, and the worker should use appropriate respiratory protection. /Antineoplastic agents/

10 minutes

The biological half-life of procarbazine hydrochloride in both plasma and CSF is approximately 1 hour. /Procarbazine hydrochloride/

... Half-life in blood after iv injection is approx 7 min.

The plasma half-life of parent drug is approximately 10 minutes.

Procarbazine is metabolized primarily in the liver and kidneys. The drug appears to be auto-oxidized to the azo derivative with the release of hydrogen peroxide. The azo derivative isomerizes to the hydrazone, and following hydrolysis splits into a benzylaldehyde derivative and methylhydrazine. The methylhydrazine is further degraded to CO₂ and CH₄ and possibly hydrazine, whereas the aldehyde is oxidized to N-isopropylterephthalamic acid, which is excreted in the urine.

It is rapidly metabolized in man ... . Oxidation of procarbazine produces the corresponding azo compound and hydrogen peroxide. Further metabolism, presumably in the liver, yields azoxy derivatives that circulate in the bloodstream and have potent cytotoxic activity.

Procarbazine yields demethylprocarbazine probably in rats; yields n-isopropyl-alpha-methylazo-p-toluamide and terephthalic isopropylamide in rats. /from table/

Rats biotransformed ip dose of (14)C-monomethylhydrazine to (14)C-methane within 3 min of injection. ... Rats produced 25% (14)C-CH4 and 3% (14)C-CO2 in 90 min. ...(14)C-procarbazine ... was less readily biotransformed to CH4. After 90 min, 4% of dose...excreted as (14)C-CH4. /hydrochloride/

The NADPH-dependent microsomal metabolism of [14C]procarbazine labeled on the terminal N-methyl group resulted in the covalent binding of the drug to exogenously added DNA; this reaction was inhibited by metyrapone. Procarbazine metabolism was also shown to result in covalent binding of the methyl group of the drug to microsomal protein upon metabolism but the extent of protein binding was at least an order of magnitude smaller than that see with its primary oxidative metabolite. N-isopropyl-alpha-(2-methylazo)-p-toluamide. The characteristics of the reactions leading to the covalent binding of the N-methyl group of the azo derivative to microsomal protein and its metabolism to form methane, possessed a number of similarities in the apparent kinetic parameters (Km and Vmax), induction and inhibition patterns indicating a common pathway of metabolism to form a reactive intermediate and the involvement of cytochrome p450. Reduced glutathione stimulated methane formation and inhibited covalent binding to protein.

For more Metabolism/Metabolites (Complete) data for PROCARBAZINE (6 total), please visit the HSDB record page.

35S93Y190K

PROCARBAZINE

Mechanisms of Action [MoA] - Alkylating Activity

Established Pharmacologic Class [EPC] - Alkylating Drug

Procarbazine is an Alkylating Drug. The mechanism of action of procarbazine is as an Alkylating Activity.

Procarbazine is rapidly and completely absorbed.

Procarbazine hydrochloride is rapidly and nearly completely absorbed from the GI tract following oral administration. Following oral administration of a single 30 mg dose of radiolabeled procarbazine hydrochloride, peak plasma radioactive concentrations of the drug were attained within 1 hour. Oral administration generally results in plasma concentrations similar to those achieved following IV administration of the drug. /Procarbazine hydrochloride/

Approximately 45% to 70% of a dose is excreted in the urine during the first 24 hr as metabolites.

From 25 to 70% of an oral or parenteral dose given to man is recovered from the urine during the first 24 hours after administration; less than 5% is excreted as the unchanged compound, and the rest is mostly in the form of a metabolite, N-isopropylterephthalanic acid.

Distribution studies in animals and humans using radiolabeled procarbazine hydrochloride administered IV have shown concentrations of radioactivity to be present in the liver, kidneys, intestinal wall and skin. The drug crosses the blood-brain barrier and distributes into CSF. Equilibration of procarbazine between plasma and CSF occurs rapidly following oral administration. It is not known whether procarbazine is distributed into milk.

For more Absorption, Distribution and Excretion (Complete) data for PROCARBAZINE (6 total), please visit the HSDB record page.