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 a 600-mg dose of radiolabeled abacavir, 82.2% of the dose is excreted in urine and 16% of the dose is excreted in feces. The 5-carboxylic acid metabolite, 5-glucuronide metabolite, and unchanged abacavir accounted for 30, 36, and 1.2%, respectively, of recovered radioactivity in urine; unidentified minor metabolites accounted for 15% of recovered radioactivity in urine.
It is not known whether abacavir is distributed into human milk; the drug is distributed into milk in rats.
Abacavir crosses the placenta in rats.
The oral bioavailability of abacavir is high with or without food; the CSF-to-plasma AUC ratio is approximately 0.3.
For more Absorption, Distribution and Excretion (Complete) data for ABACAVIR SULFATE (7 total), please visit the HSDB record page.

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Metabolism / Metabolites
Abacavir is partially metabolized by alcohol dehydrogenase (to form the 5'-carboxylic acid) and glucuronidation (to form the 5'-glucuronide).
The metabolic fate of abacavir has not been fully determined, but the drug is metabolized in the liver. Abacavir is metabolized by alcohol dehydrogenase to form the 5-carboxylic acid and by glucuronyltransferase to form the 5-glucuronide; these metabolites do not appear to have any antiviral activity. Any involvement of cytochrome p450 isoenzymes in the metabolism of abacavir is limited.
Intracellularly, abacavir is phosphorylated to abacavir monophosphate by adenosine phosphotransferase; abacavir monophosphate is then converted to carbovir monophosphate in a reaction catalyzed by cytosolic enzymes and then to carbovir triphosphate by cellular kinases. Intracellular (host cell) conversion of abacavir to carbovir triphosphate is necessary for the antiviral activity of the drug. The in vitro intracellular half-life of carbovir triphosphate in CD4+ CEM cells is 3.3 hours.

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Biological Half-Life
The in vitro intracellular half-life of carbovir triphosphate /SRP: a metabolite of abacavir sulfate,/ in CD4+ CEM cells is 3.3 hours.
The plasma elimination half-life of abacavir following a single oral dose (given as abacavir sulfate) is about 1.5 hours. In HIV-infected children 3 months to 13 years of age who received 8 mg/kg of abacavir every 12 hours (given as an oral solution containing abacavir sulfate), steady-state plasma elimination half-life averaged 1.3 hours and was essentially the same as that reported after a single dose. Following oral administration of a single 300-mg dose of abacavir to an individual with renal failure (glomerular filtration rate less than 10 mL/minute) undergoing peritoneal dialysis, the plasma elimination half-life of the drug was 1.33 hours.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Abacavir appears in breastmilk in small quantities. Very little information is available on the safety of its use during breastfeeding. Achieving and maintaining viral suppression with antiretroviral therapy decreases breastfeeding transmission risk to less than 1%, but not zero. Individuals with HIV who are on antiretroviral therapy with a sustained undetectable viral load and who choose to breastfeed should be supported in this decision. If a viral load is not suppressed, banked pasteurized donor milk or formula is recommended.
◉ Effects in Breastfed Infants
An HIV-positive mother took a combination tablet containing dolutegravir 50 mg, abacavir sulfate 600 mg and lamivudine 300 mg (Triumeq) once daily. Her infant was exclusively breastfed for about 30 weeks and partially breastfed for about 20 weeks more. No obvious side effects were noted.
◉ Effects on Lactation and Breastmilk
Gynecomastia has been reported among men receiving highly active antiretroviral therapy. Gynecomastia is unilateral initially, but progresses to bilateral in about half of cases. No alterations in serum prolactin were noted and spontaneous resolution usually occurred within one year, even with continuation of the regimen. Some case reports and in vitro studies have suggested that protease inhibitors might cause hyperprolactinemia and galactorrhea in some male patients, although this has been disputed. The relevance of these findings to nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

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Interactions
Concurrent use /of ethanol/ with abacavir may result in increased concentrations and half-life of abacavir as a result of competition for common metabolic pathways via alcohol dehydrogenase.
Methadone clearance increased 22% in patients stabilized on oral methadone maintenance therapy who started abacavir therapy with 600 mg twice daily; increase in clearance will not be clinically significant in the majority of patients; methadone dosage increase may be required in a small number of patients.

[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, in combination with other agents, for treatment of HIV-1 infection. /Included in US product labeling/

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Drug Warnings
A unique and potentially fatal hypersensitivity reaction occurs in 2% to 5% of patients receiving abacavir. Symptoms typically occur within the first six weeks of therapy and include fever, rash, nausea, malaise, and respiratory complaints, in various combinations. Symptoms initially may be mild but increase in severity with continued administration. Discontinuation of the medication usually resolves all signs and symptoms, but rechallenge may cause rapid onset of severe reactions, hypotension, and death. Once an abacavir hypersensitivity reaction is suspected or confirmed, it is recommended that the patient never by rechallenged with abacavir.
The major toxicity associated with abacavir therapy is potentially life-threatening hypersensitivity reactions. In clinical studies, hypersensitivity reactions have been reported in approximately 5% of adult and pediatric patients receiving abacavir in conjunction with lamivudine and zidovudine. Fatalities related to hypersensitivity reactions to abacavir have been reported. Manifestations of hypersensitivity usually are apparent within the first 6 weeks of abacavir therapy, but may occur at any time during therapy. Severe hypersensitivity reactions are likely to recur within hours following rechallenge in patients with a prior history of hypersensitivity to the drug, and these reactions may include life-threatening hypotension and death. The most severe hypersensitivity reactions reported to date have been in individuals who were rechallenged with abacavir after a previous hypersensitivity reaction to the drug. There also have been reports of severe or fatal hypersensitivity reactions occurring after abacavir was reintroduced in patients with no identified history of abacavir hypersensitivity or with unrecognized manifestations of hypersensitivity to the drug. Although these patients had discontinued abacavir for reasons unrelated to hypersensitivity (e.g., interruption in drug supply, discontinuance of abacavir during treatment for other medical conditions), some may have had symptoms present before discontinuance of the drug that were consistent with hypersensitivity but were attributed to other medical conditions (e.g., acute onset respiratory disease, gastroenteritis, adverse reactions to other drugs). Most of the hypersensitivity reactions reported following reintroduction of abacavir in these patients were indistinguishable from hypersensitivity reactions associated with abacavir rechallenge (i.e., short time to onset, increased severity of symptoms, poor outcome including death).Hypersensitivity reactions can occur within hours after abacavir is reintroduced; however, in some cases, these reactions occurred days to weeks following reintroduction of the drug.
Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) have been reported rarely in patients receiving abacavir and also have been reported in patients receiving dideoxynucleoside reverse transcriptase inhibitors. Most reported cases have involved women; obesity and long-term therapy with a nucleoside reverse transcriptase inhibitor also may be risk factors. Increased serum concentrations of Gamma-glutamyltransferase (GGT, GGPT) have been reported in patients receiving abacavir.
Hypersensitivity reactions reported in patients receiving abacavir are characterized by the appearance of manifestations indicating involvement of multiple organ and body systems; these reactions have occurred in association with anaphylaxis, liver failure, renal failure, hypotension, and death. The most frequent manifestations of hypersensitivity reactions to abacavir include fever, rash, fatigue, GI symptoms such as nausea, vomiting, diarrhea, and abdominal pain, and respiratory symptoms such as pharyngitis, dyspnea, and cough. Other signs and symptoms include malaise, lethargy, myalgia, myolysis, headache, arthralgia, edema, paresthesia, lymphadenopathy, and mucous membrane lesions (e.g., conjunctivitis, mouth ulceration). Respiratory symptoms, including cough, dyspnea, and pharyngitis, have been reported in approximately 20% of patients with hypersensitivity reactions to abacavir. Fatalities have occurred in patients who developed hypersensitivity reactions in which the initial presentation included respiratory symptoms; some patients who experienced fatal hypersensitivity reactions were initially diagnosed as having an acute respiratory disease (pneumonia, bronchitis, flu-like illness). Hypersensitivity reactions can occur without rash; if rash occurs, it usually is maculopapular or urticarial, but may be variable in appearance. Laboratory abnormalities reported in patients experiencing a hypersensitivity reaction to abacavir include lymphopenia and increases in serum concentrations of liver enzymes, creatine kinase (CK, creatine phosphokinase, CPK), or creatinine.
For more Drug Warnings (Complete) data for ABACAVIR SULFATE (17 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.)