Details of the Drug

General Information of Drug (ID: DMCZGRE)

Drug Name

Dolutegravir

Synonyms

1051375-16-6; GSK1349572; Tivicay; S/GSK1349572; Dolutegravir (GSK1349572); S-349572; GSK-1349572; GSK 1349572; UNII-DKO1W9H7M1; (4r,12as)-N-(2,4-Difluorobenzyl)-7-Hydroxy-4-Methyl-6,8-Dioxo-3,4,6,8,12,12a-Hexahydro-2h-Pyrido[1',2':4,5]pyrazino[2,1-B][1,3]oxazine-9-Carboxamide; CHEBI:76010; DKO1W9H7M1; Tivicay (TN); (4R,12aS)-N-[(2,4-Difluorophenyl)methyl]-3,4,6,8,12,12a-hexahydro-7-hydroxy-4-methyl-6,8-dioxo-2H-pyrido[1',2':4,5]pyrazino[2,1-b][1,3]oxazine-9-carboxamide; Dolutegravir Sodium (

Indication

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

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

419.4

Logarithm of the Partition Coefficient (xlogp)

2.4

Rotatable Bond Count (rotbonds)

3

Hydrogen Bond Donor Count (hbonddonor)

2

Hydrogen Bond Acceptor Count (hbondacc)

8

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 53.6 mgh/L [2]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 3.67 mg/L [2]
BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [3]
Clearance: The clearance of drug is 1.0 L/h []
Elimination: When a single oral dose of dolutegravir is given, nearly all complete dose is recovered in a proportion of 53% excreted unchanged in the feces and 31% excreted in urine [4]
Half-life: The concentration or amount of drug in body reduced by one-half in 14 hours [2]
Metabolism: The drug is metabolized via the glucuronidation by UGT1A1 [4]
Vd: The volume of distribution (Vd) of drug is 17.4 L [2]

Chemical Identifiers

Formula: C20H19F2N3O5
IUPAC Name: (3S,7R)-N-[(2,4-difluorophenyl)methyl]-11-hydroxy-7-methyl-9,12-dioxo-4-oxa-1,8-diazatricyclo[8.4.0.03,8]tetradeca-10,13-diene-13-carboxamide
Canonical SMILES: C[C@@H]1CCO[C@@H]2N1C(=O)C3=C(C(=O)C(=CN3C2)C(=O)NCC4=C(C=C(C=C4)F)F)O
InChI: InChI=1S/C20H19F2N3O5/c1-10-4-5-30-15-9-24-8-13(17(26)18(27)16(24)20(29)25(10)15)19(28)23-7-11-2-3-12(21)6-14(11)22/h2-3,6,8,10,15,27H,4-5,7,9H2,1H3,(H,23,28)/t10-,15+/m1/s1
InChIKey: RHWKPHLQXYSBKR-BMIGLBTASA-N

Cross-matching ID

PubChem CID: 54726191
ChEBI ID: CHEBI:76010
CAS Number: 1051375-16-6
DrugBank ID: DB08930
TTD ID: D00YZD
VARIDT ID: DR00383
INTEDE ID: DR0526
ACDINA ID: D00210

Combinatorial Drugs (CBD)

Click to Jump to the Detailed CBD Information of This Drug

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Human immunodeficiency virus Integrase (HIV IN)	TT5FH9Y	POL_HV1B1	Modulator	[5]

------------------------------------------------------------------------------------

Drug Transporter (DTP)

DTP Name	DTP ID	UniProt ID	MOA	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]

------------------------------------------------------------------------------------

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)_{Main DME}	DE4LYSA	CP3A4_HUMAN	Substrate	[7]
UDP-glucuronosyltransferase 1A1 (UGT1A1)_{Main DME}	DEYGVN4	UD11_HUMAN	Substrate	[7]

------------------------------------------------------------------------------------

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Cytochrome P450 26A1 (CYP26A1)	OTL1DFWV	CP26A_HUMAN	Gene/Protein Processing	[8]
Fibroblast growth factor 8 (FGF8)	OTFU0IUW	FGF8_HUMAN	Gene/Protein Processing	[8]
Homeobox protein Hox-B1 (HOXB1)	OTGC0EKI	HXB1_HUMAN	Gene/Protein Processing	[8]
Homeobox protein MIXL1 (MIXL1)	OT584VOQ	MIXL1_HUMAN	Gene/Protein Processing	[8]
T-box transcription factor TBX6 (TBX6)	OTW1Q8RM	TBX6_HUMAN	Gene/Protein Processing	[8]

------------------------------------------------------------------------------------

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Same Disease as Dolutegravir

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Disease	REF
Cobicistat	DM6L4H2	Minor	Decreased metabolism of Dolutegravir caused by Cobicistat mediated inhibition of UGT.	Human immunodeficiency virus disease [1C60-1C62]	[9]
-----------

Coadministration of a Drug Treating the Disease Different from Dolutegravir (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Ivosidenib	DM8S6T7	Minor	Increased metabolism of Dolutegravir caused by Ivosidenib mediated induction of CYP450 enzyme.	Acute myeloid leukaemia [2A60]	[9]
Arn-509	DMT81LZ	Major	Increased metabolism of Dolutegravir caused by Arn-509 mediated induction of UGT.	Acute myeloid leukaemia [2A60]	[10]
Troleandomycin	DMUZNIG	Minor	Decreased metabolism of Dolutegravir caused by Troleandomycin mediated inhibition of UGT.	Bacterial infection [1A00-1C4Z]	[9]
Pexidartinib	DMS2J0Z	Minor	Increased metabolism of Dolutegravir caused by Pexidartinib mediated induction of CYP450 enzyme.	Bone/articular cartilage neoplasm [2F7B]	[9]
Stiripentol	DMMSDOY	Minor	Decreased metabolism of Dolutegravir caused by Stiripentol mediated inhibition of UGT.	Epilepsy/seizure [8A61-8A6Z]	[9]
PF-06463922	DMKM7EW	Minor	Increased metabolism of Dolutegravir caused by PF-06463922 mediated induction of UGT.	Lung cancer [2C25]	[9]
Elagolix	DMB2C0E	Minor	Increased metabolism of Dolutegravir caused by Elagolix mediated induction of CYP450 enzyme.	Uterine fibroid [2E86]	[9]
-----------


⏷ Show the Full List of 7 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Sodium stearyl fumarate	E00545	23665634	lubricant
Sucralose	E00370	71485	Flavoring agent
Calcium sulfate dihydrate	E00315	24928	Desiccant; Diluent
Crospovidone	E00626	Not Available	Disintegrant
Ferric hydroxide oxide yellow	E00539	23320441	Colorant
Hypromellose	E00634	Not Available	Coating agent
Polyethylene glycol 4000	E00654	Not Available	Coating agent; Diluent; Ointment base; Plasticizing agent; Solvent; Suppository base; lubricant
Polyvinyl alcohol	E00666	Not Available	Coating agent; Emulsion stabilizing agent; Film/Membrane-forming agent
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Talc	E00520	16211421	Anticaking agent; Diluent; Glidant; lubricant
Titanium dioxide	E00322	26042	Coating agent; Colorant; Opacifying agent
Cellulose microcrystalline	E00698	Not Available	Adsorbent; Suspending agent; Diluent
--------------------


⏷ Show the Full List of 13 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Dolutegravir 25 mg tablet	25 mg	Oral Tablet	Oral
Dolutegravir 50 mg tablet	50 mg	Oral Tablet	Oral
Dolutegravir 10 mg tablet	10 mg	Oral Tablet	Oral
Dolutegravir Sodium eq 5mg base tablet for suspension	eq 5mg base	Tablet For Suspension	Oral
Dolutegravir Sodium eq 50mg base tablet	eq 50mg base	Tablet	Oral
Dolutegravir Sodium eq 25mg base tablet	eq 25mg base	Tablet	Oral
Dolutegravir Sodium eq 10mg base tablet	eq 10mg base	Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7365).
2	Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers. Antimicrob Agents Chemother. 2010 Jan;54(1):254-8. doi: 10.1128/AAC.00842-09. Epub 2009 Nov 2.
3	BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
4	Vaishnavi C: Fidaxomicin--the new drug for Clostridium difficile infection. Indian J Med Res. 2015 Apr;141(4):398-407. doi: 10.4103/0971-5916.159251.
5	Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
6	Tarascon Pocket Pharmacopoeia 2018 Classic Shirt-Pocket Edition.
7	Mechanisms of action, pharmacology and interactions of dolutegravir. Enferm Infecc Microbiol Clin. 2015 Mar;33 Suppl 1:2-8.
8	Dolutegravir Impairs Stem Cell-Based 3D Morphogenesis Models in a Manner Dependent on Dose and Timing of Exposure: An Implication for Its Developmental Toxicity. Toxicol Sci. 2021 Nov 24;184(2):191-203. doi: 10.1093/toxsci/kfab112.
9	Product Information. Tivicay (dolutegravir). ViiV Healthcare, Research Triangle Park, NC.
10	Cerner Multum, Inc. "Australian Product Information.".