What Is Fluorouracil?

Fluorouracil is a sterile solution of 5-fluorouracil dissolved in water for injection and added with sodium hydroxide. The pH of the solution is about 8.9. Fluorouracil is a congener of uracil, which is a component of ribonucleic acid. This drug works as an anti-metabolite. After being converted into effective fluorouracil deoxynucleotides in cells, the drug interferes with DNA by blocking deoxyribouridine from being converted to thymidine by intracellular thymidine synthase Synthesis. Fluorouracil can also interfere with RNA synthesis. After intravenous administration, fluorouracil was widely distributed in body fluids and disappeared from the blood within 4 hours. It is converted into nucleotides. It is preferentially taken up by actively dividing tissues and tumors, and fluorouracil easily enters the cerebrospinal fluid. About 20% are excreted from the urine as prototypes, and the rest are mostly metabolized in the liver by mechanisms that are generally metabolized to uracil. Pentafluorouracil and 6-mercaptopurine, as the earliest anticancer drugs, were extracted from sea cucumber. ^[1]

Common name: Fluorouracil

Danger code: Xn

Danger level: 22

UN Number: UN2811

This product is white or off-white crystalline or crystalline powder. in

This product is the most commonly used uracil antimetabolism drug. After a series of reactions in the body, it becomes fluorouracil deoxygenation.

Method name: Determination of Fluorouracil-Spectrophotometry

Application: This method uses spectrophotometry to determine the content of fluorouracil.

This method is applicable to fluorouracil.

Principle of the method: Take an appropriate amount of this product, add 0.1mol / L hydrochloric acid solution to make a solution containing about 10g per 1mL, and measure the absorbance at 265nm according to UV-visible spectrophotometry. The absorption coefficient (E1 m) of 2 is calculated for 552, that is, obtained.

Reagent: 0.1mol / L hydrochloric acid solution

equipment:

Since 5-FU is the first anti-metabolic drug synthesized based on certain ideas and is currently the most widely used antipyrimidine drug in clinical practice, it has a good effect on digestive tract cancer and other solid tumors.

This product is a pyrimidine-type fluoride, which belongs to an anti-metabolic antineoplastic drug. It can inhibit thymine nucleotide synthetase, block the conversion of deoxypyrimidine nucleotides to thymidine nucleus, and interfere with DNA synthesis. It also has a certain inhibitory effect on RNA synthesis.

Clinical use

1 gastrointestinal reaction with loss of appetite,

The oral absorption of this product is incomplete and difficult to predict, so it is administered by injection and quickly distributed to various tissues throughout the body after intravenous injection:

5-FU is effective for a variety of tumors such as gastrointestinal tumors,

1.

Strict inspection during medication

This product is combined with formyltetrahydrofolate or cisplatin, and its antitumor effect is obviously improved. This product also interacts with methotrexate. Fluorouracil is given first, and methotrexate is resistant later; on the contrary, methotrexate is used first, and then 4-6 hours later, fluorouracil is used to produce antitumor synergy. ^[4]

(1) Chloride: Take 1.0g of this product, add 100ml of water, heat to dissolve, let cool and filter; separate 25ml of filtrate, check according to law, and standard

(1) Take this product

Fluoroacetic acid

Chinese Pharmacopoeia 2000 Edition

Content (C ₄ H ₃ FN ₂ O ₂ ) /%: 97.0 103.0

Injection: 125mg (5ml) each; 250mg (10ml), store at 15-30 ° C, avoid freezing. If a precipitate forms, it can be warmed at 60 ° C to re-dissolve.

Tablet: 50mg. Compound

Toxicity data from literature and journals

Numbering	Toxicity type	testing method	Test object	Dosage used	Toxic effect
1	Acute toxicity	oral	Humanity	450 mg / kg / 30D	1. Gastrointestinal toxicity-other changes 2. Hematological toxicity-changes in bone marrow 3. Carcinogenicity-anti-tumor, anti-cancer activity
2	Acute toxicity	Intravenous injection	Humanity	6 mg / kg / 3D	1. Cardiotoxicity-changes in electrocardiogram 2. Cardiotoxicity-other changes 3. Lung, chest or respiratory toxicity-other changes
3	Acute toxicity	Intravenous injection	Adult woman	150 mg / kg / 17W-I	1. Hematological toxicity-hemolysis but not necessarily anemia
4	Acute toxicity	Intravenous injection	Adult male	39 mg / kg / 1D-I	1. Cardiotoxicity-changes in the coronary arteries
5	Acute toxicity	Intravenous injection	Adult woman	27 mg / kg / 4D-C	1. Cardiotoxicity-other changes
6	Acute toxicity	Intravenous injection	Adult male	122 mg / kg / 9W-I	1. Skin and accessory toxicity-dermatitis (after systemic exposure)
7	Acute toxicity	oral	Rat	230 mg / kg	Detailed effects are not reported other than lethal dose
8	Acute toxicity	Intraperitoneal injection	Rat	70 mg / kg	1. Gastrointestinal toxicity-excessive exercise, diarrhea 2. Gastrointestinal toxicity-nausea, vomiting
9	Acute toxicity	Subcutaneous injection	Rat	217 mg / kg	Detailed effects are not reported other than lethal dose
10	Acute toxicity	Intravenous injection	Rat	245 mg / kg	1. Gastrointestinal toxicity-excessive exercise, diarrhea 2. Gastrointestinal toxicity-nausea, vomiting
11	Acute toxicity	Intramuscular injection	Rat	240 mg / kg	Detailed effects are not reported other than lethal dose
12	Acute toxicity	Parenteral	Rat	500 mg / kg	Detailed effects are not reported other than lethal dose
13	Acute toxicity	Rectal injection	Rat	884 mg / kg	1. Gastrointestinal toxicity-excessive exercise, diarrhea 2. Gastrointestinal toxicity-other changes
14	Acute toxicity	oral	Mouse	115 mg / kg	Detailed effects are not reported other than lethal dose
15	Acute toxicity	Intraperitoneal injection	Mouse	100 mg / kg	Detailed effects are not reported other than lethal dose
16	Acute toxicity	Subcutaneous injection	Mouse	169 mg / kg	Detailed effects are not reported other than lethal dose
17	Acute toxicity	Intravenous injection	Mouse	81 mg / kg	Detailed effects are not reported other than lethal dose
18	Acute toxicity	Brain injection	Mouse	41600 ug / kg	1. Peripheral neurotoxicity-sensory changes 2. Eye toxicity-ptosis of the eyelid 3. Eye toxicity-not reported
19	Acute toxicity	trachea	Mouse	200 mg / kg	1. Nutritional and metabolic system toxicity-weight loss or weight loss rate
20	Acute toxicity	Not reported	Mouse	171 mg / kg	Detailed effects are not reported other than lethal dose
twenty one	Acute toxicity	oral	dog	30 mg / kg	1. Gastrointestinal toxicity-nausea, vomiting
twenty two	Acute toxicity	oral	rabbit	18900 ug / kg	1. Behavioral toxicity-muscle weakness 2. Gastrointestinal toxicity-excessive exercise, diarrhea 3. Nutrition and metabolic system toxicity-weight loss or rate of weight loss
twenty three	Acute toxicity	Intravenous injection	rabbit	15 mg / kg	1. Vascular toxicity-blood pressure height, without autonomic ganglia
twenty four	Acute toxicity	Intravenous injection	Guinea Pig	25 mg / kg	1. Vascular toxicity-blood pressure height, without autonomic ganglia
25	Acute toxicity	Parenteral	Hamster	140 mg / kg	1. Carcinogenicity-anti-tumor and anti-cancer activity
26	Chronic toxicity	oral	Rat	2520 mg / kg / 12W-I	1. Endocrine toxicity-changes in spleen weight 2. Hematological toxicity-changes in bone marrow 3. Chronic disease-related toxicity-changes in testicular weight
27	Chronic toxicity	oral	Rat	1092 mg / kg / 30D-I	1. Endocrine Toxicity-Changes in Thymus Weight 2. Hematological Toxicity-Orthocytic Anemia 3. Biochemical Toxicity-Inhibition of Transaminase Activity and Changes in Transaminases
28	Chronic toxicity	oral	Rat	6552 mg / kg / 26W-I	1. Endocrine toxicity-changes in thymus weight 2. Hepatotoxicity-changes in liver weight 3. Hematological toxicity-changes in red blood cell count
29	Chronic toxicity	oral	Rat	700 mg / kg / 40W-I	1. Nutrition and metabolic system toxicity-weight loss or weight gain rate decline 2. Hematological toxicity-changes in serum composition (such as TP, bilirubin, cholesterol) 3. Biochemical toxicity-Inhibiting transaminase activity and changing the spatial structure of transaminase
30	Chronic toxicity	oral	Rat	1283 mg / kg / 13W-C	1. Behavioral toxicity-changes in fluid intake 2. Endocrine toxicity-changes in thymus weight 3. Nutrition and metabolic system toxicity-weight loss or rate of weight loss
31	Chronic toxicity	Intraperitoneal injection	Rat	910 mg / kg / 26W-I	1. Gastrointestinal toxicity-other changes 2. Hematological toxicity-changes in red blood cell count
32	Chronic toxicity	Intraperitoneal injection	Rat	360 mg / kg / 60D-I	1. Chronic disease-related toxicity-death
33	Chronic toxicity	Intraperitoneal injection	Rat	780 mg / kg / 30D-I	1. Endocrine Toxicity-Changes in Thymus Weight 2. Hematological Toxicity-Orthocytic Anemia 3. Biochemical Toxicity-Inhibition of Transaminase Activity and Changes in Transaminases
34	Chronic toxicity	Intraperitoneal injection	Rat	2340 mg / kg / 13W-I	1. Hepatotoxicity-changes in liver weight 2. Kidney, ureter, and bladder toxicity-Changes in bladder weight 3. Hematological toxicity-Orthocytic anemia
35	Chronic toxicity	Subcutaneous injection	Rat	21 mg / kg / 7D-I	1. Hematological toxicity-changes in bone marrow 2. Hematological toxicity-changes in white blood cell count 3. Hematological toxicity-changes in platelet count
36	Chronic toxicity	Rectal injection	Rat	4920 mg / kg / 90D-I	1. Gastrointestinal toxicity-other changes 2. Endocrine toxicity-other changes 3. Nutrition and metabolic system toxicity-weight loss or weight loss rate
37	Chronic toxicity	Rectal injection	Rat	9540 mg / kg / 26W-I	1. Gastrointestinal toxicity-other changes 2. Endocrine toxicity-other changes 3. Chronic disease-related toxicity-death
38	Chronic toxicity	Subcutaneous injection	Mouse	300 mg / kg / 60D-I	1. Endocrine toxicity-changes in spleen weight 2. Chronic disease-related toxicity-death 3. Chronic disease-related toxicity-Testicular weight change
39	Chronic toxicity	oral	dog	455 mg / kg / 13W-I	1. Behavioral toxicity-affects food intake (animals) 2. Nutritional and metabolic system toxicity-weight loss or weight loss rate 3. Chronic disease-related toxicity-death
40	Chronic toxicity	oral	dog	175 mg / kg / 5W-I	1. Behavioral toxicity-convulsions or seizure thresholds affected 2. Hematological toxicity-changes in bone marrow 3. Chronic disease-related toxicity-death
41	Chronic toxicity	oral	Cat	182 mg / kg / 13W-I	1. Behavioral toxicity-affects food intake (animals) 2. Behavioral Toxicity-Ataxia 3. Behavioral Toxicity-Mental Suppression
42	Ocular toxicity	Skin surface	Humanity	84 mg / 3W
43	Mutation toxicity		Salmonella typhimurium	26 mg / L
44	Mutation toxicity		Escherichia coli	10 mg / L
45	Mutation toxicity		Escherichia coli	167 mg / L
46	Mutation toxicity		Escherichia coli	10 ug / plate
47	Mutation toxicity		Bacillus subtilis	300 ug / plate
48	Mutation toxicity		Bacillus subtilis	1 mg / L
49	Mutation toxicity		microorganism	2 mmol / L
50	Mutation toxicity		microorganism	125 mg / L
51	Mutation toxicity		microorganism	125 mg / L
52	Mutation toxicity		microorganism	1 gm / L
53	Mutation toxicity		microorganism	200 mg / L
54	Mutation toxicity		microorganism	300 mg / L
55	Mutation toxicity		microorganism	2 mmol / L
56	Mutation toxicity		microorganism	50 mg / L
57	Mutation toxicity		microorganism	400 mg / L
58	Mutation toxicity		microorganism	16 umol / L
59	Mutation toxicity	oral	Drosophila	5 mmol / L / 6H
60	Mutation toxicity		Neurospora crassa	20 ug / disc
61	Mutation toxicity		Saccharomyces cerevisiae	8 mg / L
62	Mutation toxicity		Saccharomyces cerevisiae	15 ug / L
63	Mutation toxicity		Schizosaccharomyces pombe	10 ug / L
64	Mutation toxicity	Parenteral	Insect ed	10 ug
65	Mutation toxicity	Parenteral	Insect ed	10 ug
66	Mutation toxicity		Human cells	13 mg / L
67	Mutation toxicity		Human cells	1 mmol / L
68	Mutation toxicity		Human cells	5 umol / L / 6H
69	Mutation toxicity		Human leukocyte	2600 nmol / L
70	Mutation toxicity		Human leukocyte	2600 nmol / L
71	Mutation toxicity		Human cells	20 mg / L
72	Mutation toxicity		Human cells	1 mmol / L
73	Mutation toxicity		Human cells	1 mmol / L
74	Mutation toxicity		Human cells	200 mg / L
75	Mutation toxicity		Human cells	1 umol / L
76	Mutation toxicity		Human cells	1 umol / L
77	Mutation toxicity		Human ovary	1 mg / L
78	Mutation toxicity	Skin surface	Humanity	1 pph
79	Mutation toxicity		Human cells	1 mg / L
80	Mutation toxicity		Hella cells	50 mg / L
81	Mutation toxicity		Salmonella typhimurium in humans	7 mg / kg
82	Mutation toxicity		Human lymphocyte	100 pmol / L
83	Mutation toxicity	Intraperitoneal injection	Rat	250 mg / kg
84	Mutation toxicity	Intraperitoneal injection	Rat	50 mg / kg
85	Mutation toxicity	Intraperitoneal injection	Mouse	12500 ug / kg
86	Mutation toxicity	Intraperitoneal injection	Mouse	26018 ug / kg
87	Mutation toxicity		Mouse embryo	10 umol / L / 24H
88	Mutation toxicity		Mouse bone marrow	20 umol / L
89	Mutation toxicity		Mouse bone marrow	19 umol / L
90	Mutation toxicity		Mouse lymphocyte	66 umol / L
91	Mutation toxicity	Intraperitoneal injection	Mouse	500 umol / kg
92	Mutation toxicity	Intravenous injection	Mouse	40 mg / kg
93	Mutation toxicity	oral	Mouse	40 mg / kg
94	Mutation toxicity		Mouse ascites tumor cells	40 mg / L
95	Mutation toxicity		Mouse ascites tumor cells	40 mg / L
96	Mutation toxicity	Intraperitoneal injection	Mouse	50 mg / kg
97	Mutation toxicity		Mouse leukocytes	3 mg / L
98	Mutation toxicity		Mouse leukocytes	100 mg / kg
99	Mutation toxicity		Mouse leukocytes	55 umol / L
100	Mutation toxicity		Mouse lymphocyte	500 ug / L
101	Mutation toxicity	Intraperitoneal injection	Mouse	50 mg / kg
102	Mutation toxicity	oral	Mouse	40 mg / kg
103	Mutation toxicity		Mouse embryo	100 nmol / L
104	Mutation toxicity		Mouse bone marrow	1800 nmol / L
105	Mutation toxicity		Mouse ascites tumor cells	7500 umol / L
106	Mutation toxicity		Mouse cells	1 ug / L
107	Mutation toxicity	oral	Mouse	50 mg / kg
108	Mutation toxicity	Intraperitoneal injection	Mouse	20 mg / kg
109	Mutation toxicity		Mouse ascites tumor cells	250 mg / kg
110	Mutation toxicity	Intraperitoneal injection	Mouse	50 mg / kg
111	Mutation toxicity	Intravenous injection	Mouse	50 mg / kg
112	Mutation toxicity	Intraperitoneal injection	Hamster	41 mg / kg
113	Mutation toxicity	Intraperitoneal injection	Hamster	41 mg / kg
114	Mutation toxicity		Hamster lung	1900 ug / L
115	Mutation toxicity		Mammalian cells	100 umol / L
116	Carcinogenicity	Intraperitoneal injection	Mouse	1500 mg / kg / 50W-I	1. Carcinogenicity-Carcinogenic (according to RTECS standards) 2. Lung, chest or respiratory toxicity-tumor 3. Hematological toxicity-tumor
117	Reproductive toxicity	Intravenous injection	Adult woman	150 mg / kg, 20-31 weeks after female conception	1. Reproductive toxicity-has other effects on newborns
118	Reproductive toxicity	Intravenous injection	Adult woman	240 mg / kg, 11-14 weeks after conception	1. Reproductive toxicity-abnormal development of the musculoskeletal system
119	Reproductive toxicity	oral	Rat	35 mg / kg, 7-13 days after conception	1. Reproductive toxicity-abnormal development of the musculoskeletal system
120	Reproductive toxicity	oral	Rat	175 mg / kg, 7-13 days after conception	1. Reproductive toxicity-affects litter size 2. Reproductive toxicity-fetal toxicity (such as fetal dysplasia but not death) 3. Reproductive toxicity-embryo or fetal death
121	Reproductive toxicity	Intraperitoneal injection	Rat	13500 ug / kg, 9 days after female conception	1. Reproductive toxicity-increased mortality after implantation 2. Reproductive toxicity-fetal toxicity (such as fetal dysplasia but not death) 3. Reproductive toxicity-embryo or fetal death
122	Reproductive toxicity	Intraperitoneal injection	Rat	15 mg / kg, 9 days after conception	1. Reproductive toxicity-increased mortality after implantation 2. Reproductive toxicity-embryo or fetal death 3. Reproductive toxicity-other developmental abnormalities
123	Reproductive toxicity	Intraperitoneal injection	Rat	30 mg / kg, 12 days after female conception	1. Reproductive toxicity-abnormal skull and facial development (including nose / tongue) 2. Reproductive toxicity-abnormal development of musculoskeletal system 3. Reproductive toxicity-abnormal development of gastrointestinal system
124	Reproductive toxicity	Intraperitoneal injection	Rat	30 mg / kg, 12 days after female conception	1. Reproductive toxicity-steady state abnormal development
125	Reproductive toxicity	Intraperitoneal injection	Rat	20 mg / kg, 9 days after conception	1. Reproductive toxicity-increased mortality after implantation 2. Reproductive toxicity-fetal toxicity (such as fetal dysplasia but not death) 3. Reproductive toxicity-other developmental abnormalities
126	Reproductive toxicity	Subcutaneous injection	Rat	20 mg / kg, 14 days after female conception	1. Reproductive toxicity-fetal toxicity (such as fetal dysplasia but not death)
127	Reproductive toxicity	Subcutaneous injection	Rat	30 mg / kg, 14 days after female conception	1. Reproductive toxicity-abnormal development of the musculoskeletal system
128	Reproductive toxicity	Intravenous injection	Rat	330 mg / kg, 7-17 days after conception	1. Reproductive toxicity-abnormal development of the musculoskeletal system
129	Reproductive toxicity	oral	Mouse	175 mg / kg, 7-13 days after conception	1. Reproductive toxicity-fetal toxicity (such as fetal dysplasia but not death) 2. Reproductive toxicity-abnormal development of the musculoskeletal system
130	Reproductive toxicity	oral	Mouse	245 mg / kg, 7-13 days after conception	1. Reproductive toxicity-affects litter size 2. Reproductive toxicity-embryo or fetal death
131	Reproductive toxicity	Intraperitoneal injection	Mouse	50 mg / kg, 13 days after female conception	1. Reproductive toxicity-affecting genetic material in fetal or embryonic cells
132	Reproductive toxicity	Intraperitoneal injection	Mouse	20 mg / kg, 10 days after conception	1. Reproductive toxicity-abnormal development of musculoskeletal system 2. Reproductive toxicity-abnormal development of skull and face (including nose / tongue)
133	Reproductive toxicity	Intraperitoneal injection	Mouse	20 mg / kg, 9 days after conception	1. Reproductive toxicity-increased mortality after implantation 2. Reproductive toxicity-other developmental abnormalities
134	Reproductive toxicity	Intraperitoneal injection	Mouse	30 mg / kg, 9 days after conception	1. Reproductive toxicity-abortion
135	Reproductive toxicity	Intraperitoneal injection	Mouse	10 mg / kg, 10 days after conception	1. Reproductive toxicity-abnormal ear / eye development 2. Reproductive toxicity-abnormal development of musculoskeletal system
136	Reproductive toxicity	Intraperitoneal injection	Mouse	30 mg / kg, 12 days after female conception	1. Reproductive toxicity-affect the live birth index of the newborn 2. Reproductive toxicity-affect the vitality index of the newborn (if still alive on the 4th day of birth) 3. Reproductive toxicity-reduced weight gain in newborns
137	Reproductive toxicity	Intravenous injection	Mouse	67 mg / kg, male mated 1 day ago	1. Reproductive toxicity-abnormal male spermatogenesis (including genetic material, sperm morphology, sperm motility and count)
138	Reproductive toxicity	Intramuscular injection	Hamster	24 mg / kg, 9 days after female conception	1. Reproductive toxicity-fetal toxicity (such as fetal dysplasia but not death) 2. Reproductive toxicity-abnormal skull and facial development (including nose / tongue)
139	Reproductive toxicity	Intramuscular injection	Hamster	28 mg / kg, 9 days after conception	1. Reproductive toxicity-increased mortality after implantation 2. Reproductive toxicity-abnormal development of the musculoskeletal system
140	Reproductive toxicity	Intramuscular injection	Hamster	56 mg / kg, 11 days after conception	1. Reproductive toxicity-steady state abnormal development
141	Reproductive toxicity	Intramuscular injection	Hamster	20 mg / kg, 9 days after conception	1. Reproductive toxicity-increased mortality after implantation

^[5-115]