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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5265_Библиотеки_им_академика_М_И_Перельмана.pdf
Anti-neoplastic Agent 347
IUPAC Name: 5-fluoro-1H-pyrimidine-2, 4-Dione
Properties: Fluorouracil is a white to nearly white crystalline powder; practically odorless.
It decomposes at 282°C to 283°C. It is practically insoluble in chloroform, ether and benzene;
soluble in methanol-water mixtures; sparingly soluble in water and slightly soluble in alcohol.
Uses: Fluorouracil is an antineoplastic agent used to treat multiple solid tumors including:
➢ Breast cancer
➢ Colorectal cancer
➢ Gastrointestinal cancers including: anal, esophageal, pancreas and gastric (stomach)
cancer
➢ Pancreatic cancer
➢ Head and neck cancer
➢ Unknown primary (squamous cell)
➢ Neuroendocrine tumors
➢ Thymic cancers
➢ Cervical cancer
➢ Bladder cancer
➢ Hepatobiliary cancers
Dosage Forms: Injectable solution – 50 mg/mL
Storage and Stability: It should be stored at 25°C; excursions permitted to 15°C to 30°C. It is
stable when exposed to air. The stability of 5-FU in PVC bags was unaffected by 14 days of
storage at either 4°C or 21°C. When stored in EVA reservoirs, 5-FU was stable for at least 2
weeks at 33°C and for 3 days at 4°C.
Officials:
➢ Fluorouracil, I.P.
➢ Fluorouracil Injection, I.P.
348 Text Book of Pharmaceutical Chemistry
13.1.5 Methotrexate
Brand Names: Trexall, Xatmep Metoject, Nordimet, Otrexup, Rasuvo, Reditrex
Methotrexate (MTX) is an antimetabolite and antifolate agent. It binds and inhibits the
enzyme dihydrofolate reductase, resulting in inhibition of purine nucleotide and thymidylate
synthesis and, subsequently, inhibition of DNA and RNA syntheses. A chemical structure of
Methotrexate is composed of a pteridine ring, p-aminobenzoic acid plus glutamic acid. The
structural formula is:
IUPAC Name: N-[4-[[(2,4-diamino-6-pteridinyl)methyl]methylamino]benzoyl]-L-glutamic acid.
Properties: Methotrexate occurs as yellow to orange-brown, odorless crystalline powder. It is
insoluble in water, alcohol, chloroform and ether; slightly soluble in dilute hydrochloric acid;
soluble in dilute solution of alkali hydroxides and carbonates; and practically insoluble
in water and in alcohol.
Uses: Methotrexate has been used in a wide range of neoplastic conditions including:
➢ It is indicated for treatment of breast carcinoma, head and neck cancers (epidermoid).
➢ It is used for the treatment of acute lymphocytic leukaemias, non-Hodgkin’s lymphoma,
soft-tissue and osteogenic sarcomas, and solid tumors particularly breast, lung, cervical,
and testicular carcinoma.
➢ It is indicated for treatment of cervical carcinoma, ovarian carcinoma and bladder
carcinoma.
➢ It is used for the treatment of acute lymphocytic leukemia and prophylaxis, and treatment
of meningeal leukemia and gestational choriocarcinoma.
➢ It is indicated for the treatment of autoimmune diseases which include psoriasis,
rheumatoid arthritis, Crohn’s disease and ectopic pregnancy, and for medical abortions.
Dosage Forms:
➢ Parenteral Injectable: 25 mg/mL
➢ Powder for Injection: 1 g/vial (25 mg/mL when reconstituted)
➢ Oral Tablets: 2.5 mg (of Methotrexate) Rheumatrex
➢ Tablets, film-coated: 5 mg Trexail (scored)
Storage and Stability: Kept in well closed, light resistant container in dark place. Methotrexate
sodium tablets should be protected from light and stored in well-closed containers at
15°C to 30°C. Methotrexate sodium injection and powder for injection should be protected from
light and stored at 15°C to 30°C.
Anti-neoplastic Agent 349
Officials:
➢ Methotraxate, I.P.
➢ Methotraxate Injection, I.P.
➢ Methotraxate Tablet, I.P.
13.1.6 Dactinomycin
Brand Name: Cosmegen
Dactinomycin (actinomycin D), a group of antibiotics produced by various species of
Streptomyces, is a principal component of the mixture of actinomycins produced by Streptomyces
parvullus. It is a chromonopeptide with a phenoxazine ring and two cyclic polypeptides joined to
the carboxyl group at position 2 and 9 of the phenoxazine ring. It binds to DNA and inhibits the
transcription with chain elongation more sensitive than initiation, termination, or release as a
result of impaired mRNA production and protein synthesis. The empirical formula is C
62
H
86
N
12
O
16
and the structural formula is:
Properties: Actinomycin D appears as bright red rhomboid prisms, bright red crystalline powder
or red powder. It is soluble in alcohol, propylene glycol, and water/glycol mixtures.
Uses: Dactinomycin is approved to be used alone or with other drugs to treat. It is most
commonly used in the treatment of a variety of cancers, including:
➢ Childhood rhabdomyo sarcoma
➢ Ovarian cancer
➢ Osteo sarcoma
➢ Soft tissue sarcoma
➢ Locoregional solid tumors
➢ Gestational trophoblastic neoplasm
➢ Metastatic testicular tumors
➢ Ewing’s sarcoma
➢ Wilms’ tumors
Storage: It is stored at room temperature, protected from light, humidity, and excessive heat. It
should be stored at 25°C; excursions permitted to 15°C to 30°C. Protect from light and humidity.
350 Text Book of Pharmaceutical Chemistry
Dosage Forms and Strengths:
➢ Dactinomycin for Injection, U.S.P.
➢ Injection, powder for reconstitution: 500 mcg/vial as a sterile, amorphous yellow to
orange, lyophilized powder in a single-dose vial.
13.1.7 Doxorubicin Hydrochloride
Brand Names: Adriamycin, Doxil, Myocet
Doxorubicin is an anthracycline antibiotic with antineoplastic activity. It is isolated from the
bacterium Streptomyces peucetius var. caesius, is the hydroxylated congener of daunorubicin. It
consists of the tetracyclic quinoid aglycone adriamycinone (14-hydroxydaunomycinone) linked
to the amino-sugar daunosamine.
Properties: Adriamycin hydrochloride appears as orange-red thin needles, with melting point
205°C almost odorless; hygroscopic. It is soluble in water; soluble in aqueous alcohols;
practically insoluble in acetone, benzene, chloroform, ethyl ether and petroleum ether; moderately
soluble in anhydrous methanol; and insoluble in non-polar organic solvents.
Uses: Doxorubicin is used to treat wide range of cancers including:
➢ Leukemia
➢ Hodgkin’s lymphoma
➢ Breast cancer
➢ Bladder cancer
➢ Kaposi’s sarcoma
➢ Lymphoma
➢ Acute lymphocytic leukemia
➢ Cancers of the bladder breast, stomach, lung, ovaries, thyroid, soft tissue sarcoma,
multiple myeloma, and others
Storage: Storage of doxorubicin hydrochloride injection under refrigerated conditions can result
in the formation of a gelled product. Place gelled product at room temperature 15°C to 30°C for
2 to 4 hours to return the product to a slightly viscous, mobile solution. Store all vials at 2°C to
8°C. Protect from light. Neutral aqueous solution is stable at room temperature.
Anti-neoplastic Agent 351
13.1.8 Vinblastine Sulphate
Brand Name: Velban
Vinblastine is a natural vinca alkaloids isolated from the leaves of the periwinkle plant,
Catharanthus roseus. It disrupts microtubule formation and function during mitosis, and
interferes with glutamic acid metabolism.
Properties: It occurs as odorless and hygroscopic; white to slightly yellow, amorphous or
crystalline powder. It is practically insoluble in water, petroleum and ether; and soluble in
alcohols, acetone, ethyl acetate and chloroform.
Uses: Vinblastine sulfate is approved as palliative treatment for:
➢ Hodgkin lymphoma
➢ Kaposi sarcoma
➢ Mycosis fungoides (a type of cutaneous T-cell lymphoma).
➢ Non-Hodgkin lymphoma (NHL) in adults
➢ Testicular germ cell tumors
➢ Choriocarcinoma (a type of gestational trophoblastic disease) that has not gotten better
with other chemotherapy
➢ Breast cancer that has not gotten better with other treatment
Storage and Stability: Solution may be stored in refrigerator for periods of 30 days without
significant loss of potency. Vinblastine is stored in well closed container protected from light, and
stored at a temperature between 2°C to 10°C.
Preparation: Vinblastine Sulfate 1 mg/mL solution for injection contains 35.42 mg sodium in
each 10 ml vial.
Officials:
➢ Vinblastine Sulphate, I.P.
➢ Vinblastine Sulphate Injection I.P.
13.1.9 Cisplatin
Brand Name: Platinol-AQ
Cisplatin is the prototype platinum coordination complex, an alkylating agent. It is a
diammine dichloro platinum compound in which the two ammine ligands and two chloro ligands
are oriented in a cis planar configuration around the central platinum ion.
352 Text Book of Pharmaceutical Chemistry
IUPAC Name: Azane, Dichloroplatinum
Properties: Cisplatin occurs as deep yellow solid. It is soluble in water, sodium chloride,
dimethylformamide and insoluble in most common solvents. It slowly changes from the cis to the
trans form in aqueous solution.
Uses: Cisplatin is a chemotherapy agent used to treat a number of cancers including – testicular,
ovarian, bladder and cervical cancer, breast cancer, head and neck cancer, esophageal cancer,
mesothelioma and brain tumors.
Storage Conditions: Store under refrigeration (2°C to 8°C) and protect from light. Cisplatin
solution should be stored between 15°C and and 25°C, and protect from light.
13.1.10 Dromostanolone Propionate
Brand Names: Drolban, Masteril, Masteron, Mastisol, Metormon, Permastril, Prometholone.
Dromostanolone Propionate (also known as Drostanolone) is the propionate salt form of
dromostanolone, a synthetic anabolic/androgenic steroid derived from dihydrotestosterone
(DHT). The backbone of DHT has been modified with a 2-methyl group at the C2α position to
increase its anabolic properties. Dromostanolone inhibits the growth of estrogen receptor-
presenting breast cancers. It is not active via the oral route and must be administered via
intramuscular injection. Drostanolone propionate is metabolized into Drostanolone.
Properties: It occurs as white solid powder. Its melting point is 114°C to 120°C. It is soluble in
DMSO, not in water.
Uses:
➢ An anabolic steroid is used as an antineoplastic.
➢ It is an androgen and anabolic steroid (AAS) medication indicated in post-menopausal
women with recurrent breast cancer, in a combined hormone therapy.
➢ It is given by injection into muscle. This has also been used non-medically for physique-
or performance-enhancing purposes.
Storage Condition: Dry, dark and at 0°C to 4°C for short term (days to weeks) or –20°C for long
term (months to years), controlled substance, –-20°C freezer. Vials for parenteral administration
should be stored at room temperature (15°C to 30°C). Visual inspection or particulate and/or
discoloration are advisable.
Anti-neoplastic Agent 353
13.2 EXERCISE
A. Long Answer Type Questions
1. What are anticancer agents? Classify them and give the structure and uses of
Cyclophosphamide.
2. What are antimetabolites? Give examples and discuss two of them in detail.
3. Write the structure, properties and medicinal uses of Fluorouracil.
4. Give structure, properties and uses of:
(a) Busulfan
(b) Mercaptopurine
5. Give structure, properties, uses and official preparations of Methotraxate.
B. Short Answer Type Questions
1. Define cancer.
2. What are alkylating agents?
3. What is carcinoma?
4. Write the properties of Mercaptopurine.
5. Give the uses of Vinblastine Sulphate.
6. Write the brand name, structure, uses and storage of Doxorubicin hydrochloride.
7. Write the difference between Benign tumor and Malignant tumor.
8. What do you mean by the term leukemia and sarcoma?
C. Fill in the Blanks
1. Brand name of Doxorubicine hydrochloride is __________.
2. Florouracil is __________ analogue.
3. Chlorambucil is __________ derivative.
4. Vincristine and Vinblastine are __________.
5. Dromostanolone Propionate is also known as __________.
6. Vinblastine is isolated from the leaves of the __________.
7. Dactinomycin is also known as __________.
8. The popular brand name of Cisplatin is __________.
354 Text Book of Pharmaceutical Chemistry
Answers:
1. Adriamycin
2. Pyrimidine analogue
3. Nitrogen mustard
4. Vinca alkaloid
5. Drostanolone
6. Periwinkle plant, Catharanthus roseus
7. Actinomycin D
8. Platinol-AQ
