Details of the Drug

General Information of Drug (ID: DMMN36E)

Drug Name

Abacavir

Synonyms

Trizivir; Ziagen; Abacavir [INN]; Abacavir (INN); Ziagen (TN); Ziagen (TM)(*Succinate salt*); [(1S,4R)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]cyclopent-2-en-1-yl]methanol; {(1S-cis)-4-[2-amino-6-(cyclopropylamino)-9H-purin-9-yl]cyclopent-2-en-1-yl}methanol; (+/-)-4-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol; (+/-)-Abacavir; (1S,4R)-4-[2-Amino-6-(cyclopropylamino)-9H-purin-9-yl]-2-cyclopentene-1-methanol; ABC

Indication

Disease Entry	ICD 11	Status	REF
Human immunodeficiency virus infection	1C62	Approved	[1]
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Therapeutic Class

Anti-HIV Agents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

286.33

Logarithm of the Partition Coefficient (xlogp)

0.9

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 6.02 +/- 1.73 mgh/L []
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 3.0 +/- 0.89 mg/L []
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
Bioavailability: The bioavailability of drug is 83% []
Clearance: The drug present in the plasma can be removed from the body at the rate of 13 mL/min/kg [3]
Elimination: 1.2% of drug is excreted from urine in the unchanged form [2]
Half-life: The concentration or amount of drug in body reduced by one-half in 1.54 +/- 0.63 hours [3]
Metabolism: The drug is metabolized via the hepatic []
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 29.9345 micromolar/kg/day [4]
Unbound Fraction: The unbound fraction of drug in plasma is 0.5% [3]
Vd: The volume of distribution (Vd) of drug is 0.86 +/- 0.15 L/kg []
Water Solubility: The ability of drug to dissolve in water is measured as 77 mg/mL [2]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Hypersensitivity	rs2395029	HCP5	OTV0YRI8	[5]
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Chemical Identifiers

Formula: C14H18N6O
IUPAC Name: [(1S,4R)-4-[2-amino-6-(cyclopropylamino)purin-9-yl]cyclopent-2-en-1-yl]methanol
Canonical SMILES: C1CC1NC2=C3C(=NC(=N2)N)N(C=N3)[C@@H]4C[C@@H](C=C4)CO
InChI: 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
InChIKey: MCGSCOLBFJQGHM-SCZZXKLOSA-N

Cross-matching ID

PubChem CID: 441300
ChEBI ID: CHEBI:421707
CAS Number: 136470-78-5
DrugBank ID: DB01048
TTD ID: D0A4IJ
VARIDT ID: DR00588
INTEDE ID: DR0027
ACDINA ID: D00002

Combinatorial Drugs (CBD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human immunodeficiency virus Reverse transcriptase (HIV RT)	TT84ETX	POL_HV1B1	Inhibitor	[6]

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Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[7]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[8]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[9]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Substrate	[10]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Substrate	[11]
Alcohol dehydrogenase class-V (ADH6)	DE017IC	ADH6_HUMAN	Substrate	[10]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Protein Interaction/Cellular Processes	[12]
C-reactive protein (CRP)	OT0RFT8F	CRP_HUMAN	Gene/Protein Processing	[13]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Gene/Protein Processing	[14]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Gene/Protein Processing	[14]
Eyes absent homolog 1 (EYA1)	OTHU807A	EYA1_HUMAN	Gene/Protein Processing	[15]
Fibroblast growth factor 8 (FGF8)	OTFU0IUW	FGF8_HUMAN	Gene/Protein Processing	[15]
Forkhead box protein C2 (FOXC2)	OT83P1E0	FOXC2_HUMAN	Gene/Protein Processing	[15]
Glial fibrillary acidic protein (GFAP)	OTQ01ZAS	GFAP_HUMAN	Gene/Protein Processing	[16]
HLA class I histocompatibility antigen protein P5 (HCP5)	OTV0YRI8	HCP5_HUMAN	Drug Response	[5]
HLA class I histocompatibility antigen, B alpha chain (HLA-B)	OTNXFWY2	HLAB_HUMAN	Drug Response	[17]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Abacavir

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Cobicistat	DM6L4H2	Moderate	Decreased metabolism of Abacavir caused by Cobicistat mediated inhibition of CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[18]
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Coadministration of a Drug Treating the Disease Different from Abacavir (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Abacavir and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[18]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Abacavir and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[19]
Cannabidiol	DM0659E	Moderate	Increased risk of hepatotoxicity by the combination of Abacavir and Cannabidiol.	Epileptic encephalopathy [8A62]	[20]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of hepatotoxicity by the combination of Abacavir and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[21]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Abacavir and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[22]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Abacavir and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[23]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Abacavir and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[24]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Abacavir and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[25]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Abacavir and Idelalisib.	Mature B-cell leukaemia [2A82]	[26]
Orlistat	DMRJSP8	Moderate	Altered absorption of Abacavir caused by Orlistat.	Obesity [5B80-5B81]	[27]
Riociguat	DMXBLMP	Moderate	Decreased metabolism of Abacavir caused by Riociguat mediated inhibition of CYP450 enzyme.	Pulmonary hypertension [BB01]	[23]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Abacavir and Leflunomide.	Rheumatoid arthritis [FA20]	[23]
Trabectedin	DMG3Y89	Moderate	Increased risk of hepatotoxicity by the combination of Abacavir and Trabectedin.	Solid tumour/cancer [2A00-2F9Z]	[20]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Carmellose sodium	E00625	Not Available	Disintegrant
Eisenoxyd	E00585	56841934	Colorant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Hypromellose	E00634	Not Available	Coating agent
Magnesium stearate	E00208	11177	lubricant
Polyethylene glycol 400	E00653	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polysorbate 80	E00665	Not Available	Dispersing agent; Emollient; Emulsifying agent; Plasticizing agent; Solubilizing agent; Surfactant; Suspending agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Triacetin	E00080	5541	Humectant; Plasticizing agent; Solvent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Abacavir 300 mg tablet	300 mg	Oral Tablet	Oral

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References

1	Abacavir (marketed as Ziagen) and Abacavir-containing Medications. FDA. 2008.
2	BDDCS applied to over 900 drugs
3	Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4	Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
5	The HCP5 single-nucleotide polymorphism: a simple screening tool for prediction of hypersensitivity reaction to abacavir. J Infect Dis. 2008 Sep 15;198(6):864-7. doi: 10.1086/591184.
6	Quadruple nucleos(t)ide reverse transcriptase inhibitors-only regimen of tenofovir plus zidovudine/lamivudine/abacavir in heavily pre-treated HIV-1 infected patients: salvage therapy or backbone only Curr HIV Res. 2009 May;7(3):320-6.
7	Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
8	QSAR analysis and molecular modeling of ABCG2-specific inhibitors. Adv Drug Deliv Rev. 2009 Jan 31;61(1):34-46.
9	The transport of anti-HIV drugs across blood-CNS interfaces: summary of current knowledge and recommendations for further research. Antiviral Res. 2009 May;82(2):A99-109.
10	A review of the pharmacokinetics of abacavir. Clin Pharmacokinet. 2008;47(6):351-71.
11	Product characteristics of Triumeq.
12	Binding of anti-HIV drugs to human serum albumin. IUBMB Life. 2004 Oct;56(10):609-14. doi: 10.1080/15216540400016286.
13	Changes in biomarkers of cardiovascular risk after a switch to abacavir in HIV-1-infected individuals receiving combination antiretroviral therapy. HIV Med. 2009 Nov;10(10):627-33.
14	Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
15	Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
16	The antiretroviral nucleoside analogue Abacavir reduces cell growth and promotes differentiation of human medulloblastoma cells. Int J Cancer. 2009 Jul 1;125(1):235-43. doi: 10.1002/ijc.24331.
17	Genetic variations in HLA-B region and hypersensitivity reactions to abacavir. Lancet. 2002 Mar 30;359(9312):1121-2. doi: 10.1016/S0140-6736(02)08158-8.
18	Cerner Multum, Inc. "Australian Product Information.".
19	Product Information. Turalio (pexidartinib). Daiichi Sankyo, Inc., Parsippany, NJ.
20	Cerner Multum, Inc. "UK Summary of Product Characteristics.".
21	Product Information. Adcetris (brentuximab vedotin). Seattle Genetics Inc, Bothell, WA.
22	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
23	Canadian Pharmacists Association.
24	Product Information. Juxtapid (lomitapide). Aegerion Pharmaceuticals Inc, Cambridge, MA.
25	Al-Nawakil C, Willems L, Mauprivez C, et.al "Successful treatment of l-asparaginase-induced severe acute hepatotoxicity using mitochondrial cofactors." Leuk Lymphoma 55 (2014): 1670-4. [PMID: 24090500]
26	Product Information. Zydelig (idelalisib). Gilead Sciences, Foster City, CA.
27	MHRA. Medicines and Healthcare Products Regulatory Agency "Orlistat: theoretical interaction with antiretroviral HIV medicines.".