What Is Stavudine?

Stavudine, chemical name 3'-deoxy-2 ', 3'-didehydrothymidine; 3'-deoxy-2', 3'-didehydrothymidine. Colorless granular solid, melting point 165-166 ° C, melting point 174 ° C. UV maximum absorption (water): 266 nm (10149). [] D20-46.1 ° (C = 0.7, water). [] D23 -39.4 ° (C = 0.701, water) has also been reported. It is used to treat children with HIV infection from 3 months to 12 years old. The main adverse reaction was peripheral neuritis, and the incidence was dose-dependent.

Chinese name: Stavudine
Foreign name: Stavudine

Molecular formula: C10H14N2O4
Molecular weight: 226.2292
CAS number: 3056-17-5

Brief introduction of stavudine compounds

Stavudine Basic Information

Chinese name:

Chinese alias: 1- (2,3-Dideoxy--D-glycero-pent-2-enofuranosyl) thymine; 3'-deoxy-2 ', 3'-didehydrothymidine; 2', 3'-di Dehydro-3'-deoxythymidine; 2 ', 3'-didehydro-3'-deoxythymidine; 1- (2,3-Dideoxy--D-glycero-pent-2-e; Division Taffidine;

English name: stavudine

English alias: D4T; Stavudine; 2 ', 3'-Anhydrothymidine; Stavir; Sanilvudine; 2', 3'-Didehydro-3'-deoxythyMidine; sanilvudine; 2 ', 3'-dideoxy-2', 3'-didehydrothymidine; 2 ', 3'-dideoxy-2', 3'-didehydrothymine; 2 ', 3'-didehydro-3'-deoxythimidine; Stauvidine; 2', 3'-didehydro-3'-deoxythymidine; Avostav; 2 ', 3 '-Didehydro-3'-deoxythymidine; 1- (2,3-Dideoxy-Beta-D-Glycero-2-Pentenofuranosyl) Thymine; Virostav; ZERIT; 1- (2,3-Dideoxy--D-glycero-2 -pentenofuranosyl) thymine;

CAS number: 3056-17-5

MDL number: MFCD00132921

RTECS number: XP2075000

PubChem number: 24278356

Molecular formula: C ₁₀ H ₁₂ N ₂ O ₄

Structural formula:

Molecular weight: 224.21300

Exact mass: 224.08000

PSA: 84.32000

Statin physical and chemical properties

Appearance and properties: white powder

Density: 1.374g / cm3

Melting point: 159-160 ° C

Refractive index: -46 ° (C = 0.69, H2O)

Water solubility: 5-10 g / 100 mL at 21 ºC

Stability: Stable. Combustible. Incompatible with strong oxidizing agents.

Storage conditions: -20ºC

Stavudine safety information

Customs Code: 2938901000

WGK Germany: 2

Danger category code: R36 / 37/38

Safety instructions: S26-S36

RTECS number: XP2075000

Dangerous goods mark: Xi ^[1]

Stavudine molecular structure data

1. Molar refractive index: 53.85

2. Molar volume (cm / mol): 163.0

3. Isotonic specific volume (90.2K): 441.1

4. Surface tension (dyne / cm): 53.5

5. Polarizability (10cm): 21.35

Stavudine Computational Chemical Data

1. Hydrophobic parameter calculation reference value (XlogP): None

2.Number of hydrogen-bonded donors: 2

3.Number of hydrogen bond acceptors: 4

4.Number of rotatable chemical bonds: 2

5.Number of tautomers: 3

6. Topological molecular polar surface area 78.9

7.Number of heavy atoms: 16

8.Surface charge: 0

9.Complexity: 388

10.Number of isotope atoms: 0

11. Determine the number of atomic stereocenters: 2

12. Uncertain number of atomic stereocenters: 0

13. Determine the number of chemical bond stereocenters: 0

14. Uncertain number of chemical bond stereocenters: 0

15. Number of covalent bond units: 1 ^[2]

Stavudine synthesis method

Thymidine was dissolved in anhydrous pyridine, and methanesulfonyl chloride was added dropwise under cooling with ice salt, stirred, filtered, and dried under vacuum to obtain a crude sulfonylated product. The crude product was recrystallized with 90% ethanol to obtain a fine product. The sulfonylated product was dissolved in an aqueous sodium hydroxide solution and refluxed. Neutralize with hydrochloric acid, evaporate the solvent, add chloroform to the residue, filter off insoluble matter, evaporate chloroform, and crystallize with acetic acid and ethanol to obtain. Colored solid epoxy. Recrystallize twice with ethanol to obtain a white flocculent solid. This epoxy was dissolved in dimethyl sulfoxide, potassium tert-butoxide was added, and the mixture was stirred at room temperature. Neutralize to pH = 7 with 50% acetic acid in ethanol. It was concentrated under reduced pressure, and the obtained material was washed with hot acetone. The washing liquid was filtered, concentrated, and then ethanol was added to decolorize the activated carbon and filtered. The ethanol was distilled off, and a small amount of benzene was added to the rotary evaporation until the solution became cloudy, and left to stand. The precipitated solid was recrystallized from ethanol-benzene (1: 5) to obtain stavudine as a white powder. ^[2]

Stavudine use

Antiviral drugs. Its high bioavailability is expected to improve the status of anti-HIV infection. ^[2]

Stavudine Pharmacopoeia Standard

Stavudine source (name), content (potency)

This product is 1- (2,3-dideoxy--D-glyceryl-pentyl-2-enylfuranyl) thymine. Calculated as anhydrous, C10H12N2O4 should be 98.0% to 102.0%.

Stature

This product is white or off-white crystalline powder.

This product is soluble in water, slightly soluble in ethanol or acetonitrile, and almost insoluble in n-hexane.

3.5.1 Specific rotation

Take this product, weigh it accurately, dissolve it with water and dilute it quantitatively to make a solution containing 10mg per 1ml, and measure it according to law (Appendix VIE of Part Two of the Pharmacopoeia, 2010 Edition). The specific rotation is -39.5 ° to -45.9 °.

Stavudine identification

(1) In the chromatogram recorded under the relevant substance, the retention time of the main peak of the test solution should be consistent with the retention time of the stavudine peak in the mixed reference solution of the stavudine system suitability test.

(2) In the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.

(3) Take this product, dissolve and dilute it with water to make a solution containing about 10 g per 1 ml. According to ultraviolet-visible spectrophotometry (Appendix IVA of Pharmacopoeia Part II of 2010 Edition), it has the maximum absorption at a wavelength of 266nm. There is minimal absorption at a wavelength of 235 nm.

(4) The infrared light absorption spectrum of this product should be the same as that of the reference product (Appendix IV C of Part Two of the 2010 Pharmacopoeia). If they are not consistent, take this product and the reference product and recrystallize them with absolute ethanol for measurement.

The above two items (1) and (2) are optional.

Stavudine check

relative substance

Take an appropriate amount of thymine reference substance, accurately weigh it, dissolve it with water and dilute it quantitatively to make a solution containing about 250 g per 1 ml, and use it as a reference stock solution; take another product, dissolve it with water and dilute it to make it contain about 0.5 per 1 ml. A solution of mg is used as the test solution (produced by the new preparation); 1ml and 2ml of the reference stock solution are precisely measured, placed in the same 200ml volumetric flask, diluted with water to the mark, and shaken as the control solution (produced by the new preparation). According to the high performance liquid chromatography (2010 appendix D) test, using octadecylsilane bonded silica as a filler, acetonitrile-0.01mol / L ammonium acetate solution (3.5: 96.5) as the mobile phase A, Acetonitrile-0.01mol / L ammonium acetate solution (25:75) is the mobile phase B. The gradient elution is performed according to the following table. The detection wavelength is 254nm. Take an appropriate amount of the stifudine system suitability test mixed reference, dissolve and dilute with water to make a solution containing about 0.5mg per 1ml, as the system suitability test solution (the solution contains thymine, thymidine and its isomers, Stavudine and -stavudine), measure 10l into the liquid chromatograph, adjust the flow rate so that the retention time of the main peak of stavudine is between 8.5 minutes and 12.5 minutes, and the peak of thymine relative to stave The retention time of the fixed peak is about 0.28, and the retention time of the thymidine peak relative to the stavudine peak is about 0.5. The resolution of the thymidine peak and its isomer should be not less than 1.15. The stavudine peak and -staff The resolution of fixed peaks should not be less than 1.0. Measure 10 l of the control solution and inject it into the liquid chromatograph. Adjust the detection sensitivity so that the peak height of the stavudine chromatographic peak is about 10% of the full scale. Then accurately measure 10 l each of the test solution and the control solution, and inject them into the liquid chromatograph respectively to record the chromatogram. If there is an impurity peak in the chromatogram of the test solution, thymine is calculated by the peak area of the external standard method, which should not exceed 0.5%. The peak area of other single impurities should not be greater than 0.2 times (0.1%) of the main peak area of the control solution. The sum of the peak areas of impurities must not be greater than the area of the main peak of the control solution (0.5%).

Time (minutes)	Mobile phase A (%)	Mobile phase B (%)
0	100	0
10	100	0
20	0	100
30	0	100
35	100	0
40	100	0

Residual solvents- methanol, isopropanol, toluene, butyl acetate, pyridine, N, N-dimethylacetamide and N-methylpyrrolidone

Take about 0.5g of this product, weigh it accurately, add 10ml of dimethyl sulfoxide-water (1: 1), shake it to dissolve, and use it as the test solution; weigh methanol, isopropanol, toluene, and acetic acid respectively. Butyl ester, pyridine, N, N-dimethylacetamide and N-methylpyrrolidone were each diluted in dimethyl sulfoxide-water (1: 1) to make 0.15mg of methanol and isopropanol in each 1ml. A solution of 0.15 mg, 0.0445 mg of toluene, 0.15 mg of butyl acetate, 0.01 l of pyridine, 0.0545 mg of N, N-dimethylacetamide, and 0.0265 mg of N-methylpyrrolidone was shaken as a reference solution. According to the residual solvent determination method (Appendix P Third Method of Pharmacopoeia of the 2010 edition), a capillary column modified with polyethylene glycol-TPA was started at a temperature of 40 ° C for 5 minutes, and heated at a rate of 15 ° C per minute. It is maintained at 120 ° C for 2 minutes, and then heated to 200 ° C at a rate of 10 ° C per minute for 5 minutes; the inlet temperature is 150 ° C; and the detector temperature is 250 ° C. Precisely measure 1 l each of the test solution and the reference solution, inject them into the gas chromatograph, and record the chromatogram. The resolution between adjacent chromatographic peaks should meet the requirements. Calculated by the peak area based on the external standard method, the content of isopropyl alcohol and butyl acetate should not exceed 0.3%, and the others should meet the requirements.

Chloroform

Take about 0.25g of this product, and accurately weigh it. Place it in a headspace bottle, add 5ml of water and 1g of anhydrous sodium sulfate, shake well, and use it as the test solution; accurately weigh an appropriate amount of chloroform, dissolve in water and dilute it quantitatively Each 1ml contains 3g of the solution, accurately measure 5ml, place it in the headspace bottle, add 1g of anhydrous sodium sulfate, shake well, and use it as a reference solution. According to the residual solvent determination method (Appendix P of the second edition of the Pharmacopoeia of 2010 edition, the second method), a capillary column with 5% phenyl-95% methyl polysiloxane (or similar polarity) as the fixed liquid was used as the chromatography column; The temperature is 45 ° C; the inlet temperature is 150 ° C; the detector temperature is 250 ° C; the headspace bottle equilibrium temperature is 90 ° C, and the equilibration time is 30 minutes. Measure the head solution of the test solution and the reference solution, and record the chromatogram. The peak area is calculated according to the external standard method, which should meet the requirements.

Moisture

Take 0.2g of this product and measure it according to the moisture determination method (Appendix M of the second edition of the Pharmacopoeia, 2010 edition). The moisture content shall not exceed 0.5%.

Residue on ignition

Take 1.0g of this product and check it according to law (Appendix N of Part Two of the 2010 Pharmacopoeia). The residual residue shall not exceed 0.1%.

Heavy metal

Take the residue left under the burning residue and check it according to law (Appendix H, the second method of the 2010 edition of the Pharmacopoeia, the second method). The content of heavy metals must not exceed 20 parts per million.

Determination of stavudine

It was determined by high performance liquid chromatography (Appendix D, Part Two of the Pharmacopoeia, 2010 Edition).

Chromatographic conditions and system suitability tests

Octadecylsilane-bonded silica gel was used as the filler; acetonitrile-0.01mol / L ammonium acetate solution (5:95) was used as the mobile phase; the detection wavelength was 268nm. Take 5mg of thymine reference substance, 7.5mg of thymidine reference substance and 10mg of stavudine reference substance, put them in the same 100ml volumetric flask, add water to dissolve and dilute to the mark, shake well, take 10ml precisely, put in 50ml volumetric flask, Dilute with water to the mark, shake well, and use it as a system suitability test solution. Inject 10 l into the liquid chromatograph. The resolution of the thymidine peak and the thymidine peak should not be less than 3.5. .

Assay

Accurately weigh an appropriate amount of this product, add water to dissolve and quantitatively dilute it to make a solution containing 20 g per 1 ml (temporarily new). As a test solution, accurately measure 25 l, inject it into a liquid chromatograph, and record the chromatogram. Another reference substance, stavudine, was determined by the same method, and calculated by the peak area based on the external standard method. ^[3]

Stavudine Pharmacology and Toxicology

Stavudine pharmacology

Mechanism of action: Stavudine is a thymidine analog that inhibits HIV replication in human cells in vitro. Stavudine is phosphorylated by cell kinases to form the active metabolite stavudine triphosphate. Stavudine triphosphate inhibits HIV reverse transcriptase, and its mechanism includes competition with natural substrate deoxythymidine triphosphate (Ki = 0.0083-0.032M), and incorporation into viral DNA, because stavudine does not have a 3 hydroxyl group, Thereby terminating the extension of the DNA strand. Stavudine triphosphate inhibits cellular beta and gamma DNA polymerases and also significantly reduces mitochondrial DNA synthesis.

In vitro HIV sensitivity: Peripheral blood monocytes, monocytes, and lymphoblast cell lines were used to determine the antiviral activity of stavudine in vitro. For experimentally and clinically isolated HIV, the drug concentration (ED50) that inhibits virus replication by 50% ranges from 0.009 to 4 mM. In in vitro experiments, stavudine has a synergistic effect when combined with didanosine; synergistic effect when combined with zalcitabine. Stavudine is used in combination with zidovudine. Depending on the concentration ratio of the two drugs, their in vitro antiviral effects sometimes add up and sometimes antagonize. Although the sensitivity of HIV to stavudine in vitro has been established, the inhibitory effect of stavudine on HIV replication in humans is unknown.

Stavudine toxicology

Drug resistance: HIV with reduced sensitivity to stavudine has been isolated from both in vitro and stavudine-treated patients. Twenty pairs of HIV were isolated from patients treated with stavudine. A phenotypic analysis of them revealed that three of them had 4--12 times less sensitivity to stavudine. As for the genetic basis of this change in sensitivity, it has not been determined. Similarly, the clinical significance of sensitivity is unclear.

Cross-resistance: HIV was isolated from 11 patients after stavudine treatment. Five of them developed moderate resistance to zidovudine (9-176 times); three of them developed moderate resistance to didanosine e (7-29 times), and this type of cross-resistance The clinical significance is unknown.

Carcinogenicity, mutagenicity, and fertility impairment: In a two-year study of carcinogenicity, stavudine was used in mice and rats at doses 39 and 168 times the clinically recommended dose (this Multiples are based on the total absorption of both (ie, the ratio of AUC). No carcinogenic effect was found. When the dose of stavudine in mice and rats reached 250 times and 732 times the clinically recommended dose, respectively, mice Benign and malignant liver tumors appeared in rats and rats, and urinary bladder tumors appeared in male rats.

In the Ames test, E. coli reverse mutation test and CH0 / HGPRT mammalian cell forward mutation test, stavudine has no mutagenic effect with or without metabolic activation. In vitro human lymphocyte teratogenicity test, mouse fibroblast test and in vivo mouse micronucleus test, stavudine were all positive. In the absence of metabolic activation, stavudine concentrations between 25 g / ml and 250 g / ml can increase the frequency of human lymphocyte chromosome aberrations; between 25 g / ml and 250 g / ml, it can increase mouse growth. The frequency of fibroblastic transformation. In vivo micronucleus tests showed that after three days of oral administration of stavudine at 600 to 2000 mg / kg / day, bone marrow cells were mutated.

Calculated at the highest concentration (Cmax) formed by the clinical dose of 1 mg / kg / day, stavudine at 216 times did not cause fertility impairment in the rat test.

Teratogenicity phase toxicity tests were performed in rabbits and rats, respectively. When exposed to normal clinical doses of 1 mg / kg per day, 399 to 183 times (based on Cmax), there was no evidence of teratogenicity. Insufficient or terminal ossification of the sternum, when 399 times human exposure dose is given to mice-the incidence of common bone variants increases in the embryo, and no effect is observed when 216 times human exposure dose is given . When 216 times the human exposure dose was given, slight post-implant loss was seen, while when it was given close to 135 times, no effect was seen. When given a human exposure dose of 399 times, the mortality of early neonatal rats (within 4 days after birth) increased, while the survival rate of neonatal rats was not affected when the dose was close to 135 times. Studies in rats have shown that stavudine can enter the fetus through the placenta, and the drug concentration in the fetal tissue is about half the maternal plasma concentration. Human responses cannot be inferred entirely from studies of animal reproductive toxicity. ^[4]

Stavudine pharmacokinetics

The pharmacokinetics of stavudine have been studied in HIV-infected adults and children. Whether single-dose or multiple-dose administration, within the dose range of 0.03 to 4 mg / kg, the peak plasma concentration (Cmax) and area under the curve (AUC) are directly proportional to the dose. Repeated dosing every 6, 8 or 12 hours showed no significant stavudine savings.

Absorption-Absorption is rapid after oral administration, and peak plasma concentration is reached within 1 hour after administration.

Distribution-Within the concentration range of 0.01 to 11.4 g / ml, the binding of stavudine to serum proteins is weak and can be disregarded. Stavudine is equally distributed in red blood cells and plasma.

Metabolism-The metabolism of stavudine in the human body has not been elucidated.

Excretion-Regardless of the route of administration, 40% of stavudine is excreted through the kidneys. Its mean renal clearance is twice the endogenous creatinine clearance. In addition to glomerular filtration, active renal tubular secretion also exists. ^[4]

Stavudine indications

Stavudine is used in combination with other antiviral drugs to treat type I HIV infection.

Clinical use: There are several clinical studies on the combination of this product with other antiviral drugs for HIV-infected patients.

One of these is a multicenter clinical study numbered START1. This open randomized study compared 202 patients receiving first-time treatment with lamivudine and indinavir (40 mg, BID) and zidovudine plus lamivudine and indinavir. The results showed that, within 48 weeks, both the treatment of HIV RNA and the increase of CD4 cells had the same effect.

From 1992 to 1994, a randomized double-blind study, AI455-019, collected 822 cases with a series of HIV-related symptoms, and compared the efficacy of the product with zidovudine. The results showed that the two It has the same effect on HIV disease progression and death. ^[4]

Stavudine usage and dosage

Stavudine is administered at 12-hour intervals. Taking stavudine has nothing to do with meals.

Adults: The recommended dose is 40 mg twice daily for patients weighing 60 kg or more. Patients <60 kg, 30 mg once, twice daily.

Children: The recommended dosage for pediatric patients is <30 kg, 1 mg / kg each time, once every 12 hours, and for children patients> 30 kg, the recommended dosage is for adults.

Dose adjustment: If peripheral neuropathy occurs during treatment, stop stavudine treatment immediately. After stopping, the symptoms of poisoning can subside. Sometimes the symptoms of poisoning can temporarily worsen after stopping treatment. If the symptoms resolve completely, the patient can continue to tolerate the semi-recommended dose of treatment: 60 kg patients, 20 mg once, twice daily. Patients <60 kg, 15 mg once, twice daily.

After continued use of stavudine, if neuropathy recurs, consideration should be given to completely stopping stavudine treatment.

Patients with renal impairment: Patients with renal impairment who take stavudine must adjust the dosage according to the following table.

Creatinine clearance (ml / min) 60 kg <60 kg

50 40mg every 12 hours 30mg every 12 hours

26-50 20mg every 12 hours 15mg every 12 hours

10-25 40mg every 24 hours 15mg every 24 hours

Given that urinary excretion is also the main way to eliminate stavudine in pediatric patients, if renal function is impaired in pediatric patients, the clearance rate of stavudine will also change. Although there is no experimental data indicating that the dosage of these patients needs to be adjusted, it is still possible to consider reducing the dosage or extending the interval between medications.

Hemodialysis patients-The recommended dose is 20 mg (60 kg) every 24 hours, or 15 mg (<60 kg) every 24 hours, and administered after hemodialysis is complete. On non-dialysis days, it should also be given at the same time. ^[4]

Stavudine adverse reactions

Stavudine can produce peripheral neuropathy. Peripheral neuropathy is dose-related and sometimes severe. Patients with advanced HIV infection and a history of neuropathy treated with neurotoxic drugs such as didanosine are more likely to develop peripheral neuropathy. Patients need to be monitored for the toxicity of peripheral neuropathy. Peripheral neuropathy mainly manifests as tingling in hands and feet. Once the patient has this toxicity, stop using it immediately, and the symptoms of stavudine poisoning can be resolved. Sometimes the symptoms of poisoning can temporarily worsen after stopping treatment. If the symptoms resolve completely, the patient can continue to tolerate half-dose treatment. After continued use of stavudine, if neuropathy recurs, consideration should be given to completely stopping stavudine treatment.

When combined with other drugs with similar toxicity, stavudine is more likely to cause adverse reactions than stavudine alone. The incidence of adverse reactions such as pancreatitis, peripheral neuropathy, and abnormal liver function increases when stavudine is used in combination with didanosine.

The clinical study found the following adverse reactions. The items selected here are more serious and frequently reported adverse reactions.

Systemic reactions include abdominal pain, allergic reactions, chills, and fever.

The digestive system is anorexia.

Exocrine gland pancreatitis

Hematopoietic system anemia, leukocyte deficiency, and platelet deficiency.

Liver-lactic acidosis and liver steatosis, hepatitis and liver failure.

Musculoskeletal system-Muscle pain.

A nervous system insomnia.

Pediatric patients: Adverse reactions and severe laboratory abnormalities in pediatric patients are of the same type and incidence as in adults. ^[4]

Stavudine taboo

Patients who are allergic to stavudine should not use this product. ^[4]

Stavudine precautions

Stavudine is toxic to peripheral neuropathy. Patients should know that peripheral neuropathy is mainly numbness in hands and feet, and patients should tell their doctors if they notice these symptoms. Child caregivers of stavudine need to be informed by their caregivers in order to detect and report peripheral neuropathic toxicity in a timely manner.

When stavudine is used in combination with other drugs with similar toxicity to stavudine, the risk of adverse reactions may be higher than that of stavudine alone.

Stavudine cannot cure HIV infection. They still suffer from diseases caused by HIV infection, such as opportunistic bacterial infections. Patients still need to see a doctor when using stavov. In addition, taking stavudine does not prevent HIV transmission through sexual contact or blood.

HIV-infected mothers should not breastfeed their newborns to reduce postpartum HIV transmission. ^[4]

Stavudine warns:

Lactic acidosis / Severe hepatomegaly / liver failure with liver steatosis

Lactic acidosis and hepatomegaly with hepatic steatosis, including fatal cases, have been reported when used alone or in combination with nucleoside analogs including stavudine and other antiretroviral drugs. Fatal lactic acidosis has been reported in pregnant women treated with stavudine, didanosine, and antiretrovirals. Use of stavudine and didanosine during pregnancy should be used with caution and only recommended when the potential benefit is significantly greater than the harm. Liver poisoning has led to death in patients using stavudine, didanosine, and hydroxyurea. Use of stavudine in patients with known risk factors for liver disease requires special care, however, Cases without risk factors for liver disease have also been reported. Patients treated with stavudine in combination with inosine and hydroxyurea are at greater risk of developing liver poisoning than patients treated with stavudine alone and may be fatal. Patients treated with combination medication should closely monitor indicators of liver toxicity.

Phrenic peripheral neuropathy

Patients taking stavudine may develop peripheral neuropathy. Patients with advanced HIV infection, those with a history of neuropathy, and those who concurrently use drugs such as didanosine neurotoxicity are more likely to develop peripheral neuropathy.

Pancreatitis

When patients are suspected of having pancreatitis, the combined use of stavudine, didanosine (with or without hydroxyurea), and other drugs that are toxic to the pancreas should be suspended. When pancreatitis is diagnosed, re-use of stavudine should be especially careful and closely monitored for the disease ^[4]

Stavudine drug interactions

Studies have shown that stavudine has no interaction with didanosine, lamivudine and indinavir. Zidovudine can competitively inhibit intracellular stavudine phosphorylation. Zidovudine and stavudine are not recommended to be used in combination. ^[4]

Stavudine overdose

In the treatment of adults, 12 to 24 times the recommended dose has been used and no acute toxicity has been found. Complications of chronic overdose include peripheral neuropathy and liver toxicity. Stavudine can be excreted by hemodialysis. Whether stavudine can be excreted by peritoneal dialysis has not been studied. ^[4]

Stavudine expert reviews

This product is a thymine deoxynucleotide analog, which has similar anti-human immunodeficiency virus activity as zidovudine, and zidovudine-resistant HIV-1 is sensitive to this product. In a clinical trial involving 822 patients, zidovudine was administered 200 mg each time, 3 times a day or this product was 40 mg each time, twice a day for at least 6 months. Compared with the two drugs, stavudine is more effective, better tolerated, and has fewer side effects. And the course of treatment of this product can be significantly extended, up to 79 weeks; and the longest is Zidovudine for 53 weeks. According to foreign reports, a group of 33 cases of HIV-infected persons with CD4 cell counts of 400 / mm or less, including 4 cases of AIDS, 29 cases of ARC, 2, 4, 8 mg / kg per day, divided into 3 to 4 Orally, or 12 mg / kg stavudine per day, with at least 5 patients in each treatment group. The treatment effect of stavudine was shown in 6 months of treatment. The P24 antigen titer decreased in 10 of 11 patients, and the CD4 cell count increased by 50 / mm over the base in 11 of 31 patients. With a weight gain of 2.5 kg or more as a clinical improvement index, 12 of the 33 patients achieved significant clinical improvement. According to the comprehensive score of clinical symptoms, 20/30 cases improved, 17/31 cases observed improvement in biochemical indicators, and 24/33 cases achieved clinical efficacy. As of May 20, 1994, 13,000 patients had been approved for stavudine treatment by the US FDA's Parallel Tack. In a clinical trial involving 822 patients, zidovudine was used 200 mg each time, 3 times a day or this product was 40 mg each time, twice a day for at least 6 consecutive months. Compared with the two drugs, Stavudine is more effective, more tolerated, and has fewer adverse reactions. And the course of treatment of this product can be significantly extended, up to 79 weeks; and the longest is Zidovudine for 53 weeks. The dose study conclusion of this product shows that the dosage for adults should be 40mg each time, twice a day; the dosage for children should be within the range of 0.125-4mg / kg per day. There were 38 children who used this product for 12 to 36 months, with an average dosage of 2 mg / kg per day. The effect was good without drug-related adverse reactions. Adults with severe HIV infection who continued to take the drug at an adult dose for 22 weeks also achieved good clinical results. At present, with the approval of the US FDA, stavudine has been used clinically in the United States for some HIV-infected adults who have been taking zidovudine for a long time. ^[5]