In prostate cancer cell lines, abacavir hydrochloride (15 and 150 μM, 0-120 h) suppresses cell growth, modifies the expression of LINE-1 mRNA, influences the development of the cell cycle, and promotes senescence[1]. Cell migration and invasion are greatly inhibited by abacavir hydrochloride (15 and 150 μM, 18 h)[1]. Apoptosis in fat is induced by abacavir hydrochloride[4].

Abacavir hydrochloride dose-dependently promotes thrombus formation at 100 and 200 mg/kg, po; 4 h[2]. The combination of 0.1 mg/kg/d Decitabine and 50 mg/kg/d Abacavir hydrochloride (i.p.; 14 days) improves the survival of high-risk mice harboring medulloblastoma[3].

Animal/Disease Models: Male mice (9-weeks old, 22-30 g) - wild-type (WT) C57BL/6 or homozygous knockout (P2rx7 KO, B6.129P2-P2rx7tm1Gab /J)[2]
Doses: Route 1: 2.5, 5, and 7.5 μg/mL, 100 μL Route 2: 100 and 200 mg/kg
Route of Administration: Intrascrotal or oral administration for 4 h
Experimental Results: Dose-dependently promoted thrombus formation.

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Animal/Disease Models: NSGTM mice, patient-derived xenograft (PDX) cells of non-WNT/non-SHH, Group 3 and of SHH/ TP53-mutated medulloblastoma[3]
Doses: 50 mg/kg/d with 0.1 mg/kg/ d Decitabine
Route of Administration: intraperitoneal (ip)injection, daily for 14 days
Experimental Results: Inhibited tumor growth and enhanced mouse survival.

Absorption, Distribution and Excretion
Following oral administration of 600 mg of radiolabeled abacavir, 82.2% of the dose was excreted in the urine and 16% in the feces. Of the radioactive material recovered in the urine, 30% was from the 5-carboxylic acid metabolite, 36% from the 5-glucuronide metabolite, and 1.2% from the unchanged abacavir; unidentified minor metabolites accounted for 15% of the radioactive material recovered in the urine. It is unclear whether abacavir is distributed into human milk; however, it is distributed into breast milk in rats. Abacavir crosses the rat placenta. Abacavir has high oral bioavailability, regardless of food intake. The cerebrospinal fluid to plasma AUC ratio is approximately 0.3. For more complete data on the absorption, distribution, and excretion of abacavir sulfate (7 metabolites), please visit the HSDB record page.

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Metabolism/Metabolites
Abacavir is partially metabolized by alcohol dehydrogenase (to produce 5'-carboxylic acid) and glucuronidation (to produce 5'-glucuronide).
The metabolic pathway of abacavir is not fully understood, but the drug is metabolized in the liver. Abacavir is metabolized by alcohol dehydrogenase to produce 5'-carboxylic acid, and by glucuronidase to produce 5'-glucuronide; these metabolites do not appear to have any antiviral activity. Cytochrome P450 isoenzymes are involved in abacavir metabolism to a limited extent.
Intracellularly, abacavir is phosphorylated by adenosine phosphotransferase to abacavir monophosphate; abacavir monophosphate is then converted to carbovir monophosphate by cytoplasmic enzymes, and then to carbovir triphosphate by cellular kinases. The intracellular (host cell) conversion of abacavir to carbovir triphosphate is necessary for the drug to exert its antiviral activity. In vitro experiments showed that the intracellular half-life of carbovir triphosphate (SRP: a metabolite of abacavir sulfate) in CD4+ CEM cells was 3.3 hours.
Biological half-life
In vitro experiments showed that the intracellular half-life of carbovir triphosphate (SRP: a metabolite of abacavir sulfate) in CD4+ CEM cells was 3.3 hours.
The plasma elimination half-life after a single oral dose of abacavir (administered as abacavir sulfate) was approximately 1.5 hours. In HIV-infected children aged 3 months to 13 years, the steady-state plasma elimination half-life after receiving 8 mg/kg abacavir every 12 hours (administered as an oral solution containing abacavir sulfate) was on average 1.3 hours, essentially the same as the half-life after a single dose. In patients with renal failure (glomerular filtration rate less than 10 mL/min) undergoing peritoneal dialysis, the plasma elimination half-life of the drug after a single oral dose of 300 mg abacavir was 1.33 hours.

Effects During Pregnancy and Lactation
◉ Overview of Lactation Use
Abacavir is present in small amounts in breast milk. Information on the safety of abacavir during lactation is very limited. Achieving and maintaining viral suppression through antiretroviral therapy can reduce the risk of breast milk transmission to below 1%, but not zero. For HIV-infected individuals receiving antiretroviral therapy with a persistently low viral load, breastfeeding should be encouraged if chosen. If viral load is not suppressed, pasteurized donor breast milk or formula is recommended.
◉ Effects on Breastfed Infants
An HIV-positive mother took a once-daily combination tablet (Triumeq) containing 50 mg dolutegravir, 600 mg abacavir sulfate, and 300 mg lamivudine. Her infant was exclusively breastfed for approximately 30 weeks, followed by partial breastfeeding for approximately 20 weeks. No significant side effects were observed.
◉ Effects on Lactation and Breast Milk
Gynecomastia has been reported in men receiving highly active antiretroviral therapy. Gynecomastia initially occurs unilaterally, but about half of the cases progress to bilateral gynecomastia. No changes in serum prolactin levels have been observed, and it usually resolves spontaneously within one year even with continued treatment. Some case reports and in vitro studies suggest that protease inhibitors may cause hyperprolactinemia and galactorrhea in some male patients, but this conclusion remains controversial. The implications of these findings for lactating women are unclear. For mothers who have established lactation, prolactin levels may not affect their ability to breastfeed.

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Drug Interactions
Concomitant administration of ethanol and abacavir may lead to an increase in abacavir concentration and half-life due to their competition for the common metabolic pathway via alcohol dehydrogenase. In patients with stable conditions who were receiving oral methadone maintenance therapy, methadone clearance increased by 22% after starting abacavir (600 mg twice daily); for most patients, the increase in clearance was not clinically significant; a small number of patients may require an increase in the methadone dose.

[1]. The reverse transcription inhibitor abacavir shows anticancer activity in prostate cancer cell lines. PLoS One. 2010 Dec 3;5(12):e14221.

[2]. Abacavir Induces Arterial Thrombosis in a Murine Model. J Infect Dis. 2018 Jun 20;218(2):228-233.

[3]. Enhanced Survival of High-Risk Medulloblastoma-Bearing Mice after Multimodal Treatment with Radiotherapy, Decitabine, and Abacavir. Int J Mol Sci. 2022 Mar 30;23(7):3815.

[4]. Improvements in lipoatrophy, mitochondrial DNA levels and fat apoptosis after replacing stavudine with abacavir or zidovudine. AIDS. 2005 Jan 3;19(1):15-23.

Therapeutic Uses
Abacavir is indicated for the treatment of HIV-1 infection when used in combination with other medications. /US product label contains/

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Drug Warnings A unique, potentially fatal hypersensitivity reaction occurs in 2% to 5% of patients receiving abacavir. Symptoms typically appear within the first six weeks of treatment and include fever, rash, nausea, fatigue, and respiratory symptoms, with varying combinations. Symptoms may initially be mild but worsen with continued use. Discontinuation of the drug usually resolves all signs and symptoms, but re-administration can lead to a rapid onset of severe reactions, hypotension, or even death. If an abacavir hypersensitivity reaction is suspected or confirmed, patients are advised never to use abacavir again.
The main toxicity of abacavir treatment is potentially life-threatening hypersensitivity. Clinical studies have shown that approximately 5% of adult and pediatric patients receiving abacavir in combination with lamivudine and zidovudine have reported hypersensitivity reactions. There have been reports of deaths related to abacavir hypersensitivity reactions. Hypersensitivity reactions typically occur within the first 6 weeks of abacavir treatment, but can also occur at any time during treatment. In patients with a history of hypersensitivity to this drug, severe hypersensitivity reactions are likely to recur within hours of re-administration of abacavir, and these reactions can include life-threatening hypotension and death. The most severe hypersensitivity reaction reported to date occurred in a patient who had a history of hypersensitivity to this drug and was re-administered abacavir. Furthermore, severe or fatal hypersensitivity reactions have been reported in patients with no prior history of abacavir hypersensitivity or with unidentified symptoms of hypersensitivity. Although these patients discontinued abacavir for reasons unrelated to hypersensitivity (e.g., drug supply interruption, discontinuation of abacavir during treatment of other diseases), some patients may have experienced symptoms consistent with hypersensitivity before discontinuation, but these symptoms were attributed to other diseases (e.g., acute respiratory illness, gastroenteritis, adverse reactions to other drugs). Most hypersensitivity reactions reported after re-administration of abacavir are indistinguishable from those caused by re-administration of abacavir (i.e., short onset of action, worsening of symptoms, poor prognosis, and even death). Hypersensitivity reactions can occur within hours of re-administration of abacavir; however, in some cases, these reactions occur within days to weeks after re-administration of the drug. Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) have been reported in patients treated with abacavir, and have also been reported in patients treated with dideoxynucleoside reverse transcriptase inhibitors. Most reported cases are in women; obesity and long-term use of nucleoside reverse transcriptase inhibitors may also be risk factors. Elevated serum gamma-glutamyl transferase (GGT, GGPT) levels have been reported in patients treated with abacavir. Hypersensitivity reactions reported in patients treated with abacavir are characterized by symptoms suggesting involvement of multiple organs and systems; these reactions have been associated with anaphylactic shock, liver failure, kidney failure, hypotension, and death. The most common manifestations of abacavir hypersensitivity include fever, rash, fatigue, gastrointestinal symptoms (such as nausea, vomiting, diarrhea, and abdominal pain), and respiratory symptoms (such as pharyngitis, dyspnea, and cough). Other signs and symptoms include malaise, drowsiness, myalgia, rhabdomyolysis, headache, arthralgia, edema, paresthesia, lymphadenopathy, and mucosal damage (such as conjunctivitis and oral ulcers). Approximately 20% of patients with abacavir hypersensitivity report respiratory symptoms, including cough, dyspnea, and pharyngitis. Some patients may die if their initial presentation is respiratory symptoms when they develop a hypersensitivity reaction; some patients who experience fatal hypersensitivity reactions are initially diagnosed with an acute respiratory illness (pneumonia, bronchitis, influenza-like illness). Hypersensitivity reactions may also occur without a rash. If a rash does occur, it is usually a maculopapular rash or urticaria, but the appearance may vary. Laboratory abnormalities reported by patients who have developed hypersensitivity to abacavir include lymphopenia and elevated serum liver enzymes, creatine kinase (CK, creatine phosphokinase, CPK), or creatinine levels. For more complete data on drug warnings for abacavir sulfate (17 in total), please visit the HSDB record page.

C28H38N12O6S

670.74312

670.276

136777-48-5

Abacavir;136470-78-5;Abacavir sulfate;188062-50-2;Abacavir monosulfate;216699-07-9

441384

White to off-white solid

3.921

8

16

8

47

496

4

S(=O)(=O)(O)O.OC[C@@H]1C=C[C@@H](C1)N1C=NC2C1=NC(N)=NC=2NC1CC1.OC[C@@H]1C=C[C@@H](C1)N1C=NC2C1=NC(N)=NC=2NC1CC1

MCGSCOLBFJQGHM-SCZZXKLOSA-N

InChI=1S/C14H18N6O/c15-14-18-12(17-9-2-3-9)11-13(19-14)20(7-16-11)10-4-1-8(5-10)6-21/h1,4,7-10,21H,2-3,5-6H2,(H3,15,17,18,19)/t8-,10+/m1/s1

[(1S,4R)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]cyclopent-2-en-1-yl]methanol

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)