Chemical name 9-( 1, 3- dihydroxy -2- propoxymethyl)-guanine.
Pinyin name Gengxiluowei
English name ganciclovir
CASNo.: 824 10-32-0
The molecular formula is C9H 12N5O4.
Molecular weight 255.23
Specification 0.25g.
Drug name ganciclovir
Drug aliases Semiway and Li Kewei.
The chemical name of this product is 9-( 1, 3- dihydroxy -2- propoxymethyl) guanine.
Specification: Each bottle contains 540 mg of freeze-dried white or nearly colorless sodium salt powder, equivalent to 500 mg of propoxyguanosine. With 10 mL water for injection, a solution of 50 mg/mL can be prepared, and the pH value is 1 1.
Pharmacology and toxicology: intracellular deoxyguanosine is phosphorylated by deoxyguanosine kinase into monovalent phosphate of deoxyguanosine, and can also be further phosphorylated into trivalent phosphate by some cell kinases. In cells infected by cytomegalovirus, deoxyguanosine can be preferentially phosphorylated. The metabolism of trimethoprim trivalent phosphate is very slow, and it can be preserved by 60 ~ 70% after being separated from extracellular fluid 18 hours. The mechanism of inhibiting viral DNA synthesis is 1. Competitive inhibition of the binding of trivalent phosphate of deoxyguanosine to DNA polymerase, 2. The combination of trivalent nitrate of propoxyguanosine with viral DNA eventually leads to the cessation of DNA extension. It is found that patients infected with cytomegalovirus can develop acute drug resistance after treatment with this drug. Propoxyguanosine is a chemically synthesized guanine analogue, which can prevent the replication of herpes virus. Viruses sensitive to it include CMV, HSV- 1, HSV-2, EBV and VZV. Clinical research is limited to the evaluation of the curative effect of patients with cytomegalovirus infection.
Pharmacokinetics The drug is excreted in its original form mainly through glomerular filtration. In patients with normal renal function, after continuous injection of 1 hr at a dose of 5 mg/kg body weight, the half-life is 2.9 hr, and the average clearance rate is 3.64 mL/ min /kg body weight. At the dose of 5 mg/kg body weight, it was injected twice a day, and there was no drug accumulation after 14 days. The serum creatinine level of patients with renal insufficiency is
Indications are used to prevent and treat cytomegalovirus infection in immunocompromised patients, such as AIDS patients, tumor patients receiving chemotherapy, organ transplant patients using immunosuppressants, etc.
The most common adverse reactions are leukopenia and thrombocytopenia, and the rare ones are anemia, fever, rash, abnormal liver function, edema, infection and fatigue. Arrhythmia, high/low blood pressure. Abnormal thinking or nightmare, ataxia, coma, dizziness, headache, tension, sensory disturbance, psychosis, drowsiness and tremor. Nausea, vomiting, diarrhea, gastrointestinal bleeding, abdominal pain. Eosinophilia, hypoglycemia. Difficulty in breathing. Hair loss, itching, urticaria. Hematuria and elevated urea nitrogen. Retinal detachment can occur in AIDS patients with cytomegalovirus-infected retinitis. Infection, pain and phlebitis can be seen at the injection site.
The interaction between probenecid and other drugs that can inhibit renal tubular secretion and reabsorption can reduce the clearance rate of the drug through the kidney and prolong its half-life. When used with drugs that inhibit rapid cell division and replication, this drug can produce synergy. The combination of this product with dapsone, pentamidine, fluorocytosine, vincristine, vinblastine, adriamycin, amphotericin, trimethoprim and some nucleoside drugs can increase the occurrence of side effects. Most AIDS patients who use this drug and zidovudine at the same time will have severe leukopenia. This product combined with Imipenem/cilastatin sodium salt can induce epilepsy.
Usage and Dosage Treatment, prevention and induction period of cytomegalovirus infection: 5 mg/kg body weight/time, twice a day, and each injection time should exceed 1 hr for 14-2 1 day. Maintenance period: 6 mg/kg body weight/day, 5 days per week or 5 mg/kg body weight/day, 7 days per week, intravenous injection. When the patient's retinitis develops further, it is necessary to use the induced dose again for treatment.
The preventive induction dose of cytomegalovirus infection was 5 mg/kg body weight, and it was injected 1 needle every 12 hours for 7- 14 days.
When the patient has renal insufficiency, the induction dose should be adjusted to 1.25 mg/kg body weight, 1 time/day when the serum creatinine is 398μ mol/L. The optimal maintenance dose is not clear, and the dose for dialysis patients is 1.25 mg/kg body weight/day. Take the medicine immediately after dialysis for one day. Symptoms A one-time intravenous injection of 500 mg/kg to animals can cause vomiting, excessive saliva secretion, bleeding, late pregnancy, abnormal liver function, increased urea nitrogen, testicular atrophy and death. Treating hemodialysis and increasing fluid replacement can reduce the blood concentration of drugs. Each bottle should be added with 10 mL water for injection, and the concentration of its prepared solution is 50 mg/mL. Add the drug into 100 mL intravenous injection for more than1hr. 0.9% normal saline, 5% glucose, sodium lactate injection and ringer's solution can be compatible with this drug, and the antibiotic solution containing paraben can be compatible with this drug. The diluted injection should be refrigerated but not frozen, and must be used within 24 hours.
Precautions: pregnant women and lactating women are forbidden to use this medicine or are allergic to acyclovir. Preclinical studies on carcinogenesis, teratogenesis and its effect on fertility found that this product can cause sperm reduction, mutation, teratogenesis and carcinogenesis, and contraceptive measures should be taken within 90 days after stopping taking the drug. About 10 ~ 40% of the patients treated have leukopenia, so patients with a history of leukopenia should use this product with caution. 65,438+00% of patients treated with this drug had thrombocytopenia (less than 50,000/L), and the decline of patients treated with immunosuppressive drugs was even lower than that of AIDS patients. When the patient's platelet count is lower than 654.38+ 10,000 /L, the risk of thrombocytopenia also increases.
Effects on Pregnancy and Breastfeeding Animal experiments have found that this medicine has teratogenic effect and pregnant women can't use it. This medicine will have a bad effect on the offspring of mammals. At present, it is not known whether this medicine can be secreted into human milk, so it cannot be used for lactating women. It will take 72 hours to resume breastfeeding.
The clinical experience of applying it to children under 12 years old is limited, so children should use it with caution. It is reported that its adverse consequences are similar to those of adults.
The impact on the elderly should be adjusted according to renal function.
manufacturer
Shanghai Roche pharmaceutical co., ltd
manufacturing method
Many synthetic methods of ganciclovir have been reported in the literature, but the basic synthetic principle is the same. Since 1982, many companies have applied for the patent of the synthetic process of ganciclovir, but it is basically made by condensation of purine and its derivatives with various protected 2- hydroxymethylglycerol, and then deprotection. It has also been reported that ganciclovir was prepared by cyclization reaction, but the raw materials for synthesizing ganciclovir by cyclization route are scarce, the process conditions are complex and the yield is low, which has lost its industrial significance.
According to the difference of main raw materials, there are five main methods to synthesize ganciclovir, namely, Canadian EMBIO Company, American Syntex Company, American Merck Company, British Wellcome Fund Co., Ltd. and Spanish INK Company.
The chemical name of acyclovir is 9-(2- hydroxyethyl methyl) guanine.
Pinyin name Asiluowai
English name acyclovir tablets
Molecular formula C8H 1 1N5O3.
Molecular weight 225.2 1
Meter 0. 1 g
Indications: Used for skin and mucous membrane infections caused by herpes zoster virus and herpes simplex virus.
Pharmacological effects are mainly anti-herpes virus, especially anti-herpes simplex virus (HSV) types I and II, but the effect on herpes zoster virus is poor (8~ 10 times weaker). It can also inhibit EB virus. Only high concentration can inhibit cytomegalovirus (CMW).
Pharmacokinetics The oral absorption of acyclovir is only 65,438+0.5% ~ 37%, and its bioavailability is low. After intravenous drip, the blood drug concentration can be significantly increased. Plasma protein binding rate is low, and it is easy to penetrate biofilm. The concentration of cerebrospinal fluid and aqueous humor of eyeball can reach 1/3~ 1/2 of plasma concentration. Part of it is metabolized by the liver and mainly excreted from the kidney in its original form. Normal renal function is 2.5 hours.
Mechanism of Action and Drug Resistance Acyclovir is catalyzed by viral thymidine kinase (TK enzyme) and kinase in infected cells to produce Acyclovir triphosphate, which inhibits viral DNA polymerase. In addition, once acyclovir triphosphate is incorporated into the expanding DNA of the virus, DNA synthesis will be suspended. Drug-resistant virus strains have been found in clinic and experiment, and the formation of drug resistance is related to the gene mutation of viral thymidine kinase.
Clinical application is mainly used for various infections caused by herpes simplex virus, and can be used for primary or recurrent skin, mucous membrane, external genital infection and HSV infection in immunocompromised people. As the first choice for treating herpes simplex encephalitis, it is superior to cytarabine in reducing morbidity and mortality. It can also be used for herpes zoster, EB virus, and infections such as chickenpox and herpes zoster complicated by immunodeficiency. It is only used locally on the skin, and acyclovir is less absorbed by the skin.
Except for occasional dizziness, vomiting and headache, oral acyclovir is almost nontoxic and well tolerated by intravenous injection. Only 65,438+0% patients will have encephalopathy, and high-dose intravenous injection will cause nervous system disorder. Acute tubular necrosis can occur after large dose of sudden injection.
Administration and dosage by oral administration. 0.2g once, 5 times a day (every 4 hours during the day 1 time), and 5 ~ 10 days is a course of treatment.
Contraindications are prohibited for people who are allergic to this product and pregnant women.
Precautions: People with renal insufficiency, children and lactating women should use it with caution according to the doctor's advice and drink plenty of water during taking the medicine.
Store tightly.
The validity period is tentatively set at two years.
Adjustment of intravenous dose of acyclovir in patients with renal insufficiency
Creatinine clearance rate (ml/
& gt50 100 8
25~50 100 12
10~25 100 24
0~ 10 (medication after hemodialysis) 50 24
Note: Data from the case report database of National Adverse Drug Reaction Monitoring Center show that acute renal function damage caused by acyclovir and hematuria caused by cefradine are still outstanding.