Details of the Drug

General Information of Drug (ID: DM6MDCF)

Drug Name

Oliceridine

Synonyms

TRV130A

Indication

Disease Entry	ICD 11	Status	REF
Acute pain	MG31	Approved	[1]
Thyroid disease	5A00-5A06	Clinical trial	[2]

Drug Type

Small molecular drug

Structure

3D MOL is unavailable

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

386.6

Topological Polar Surface Area (xlogp)

3.5

Rotatable Bond Count (rotbonds)

7

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

5

ADMET Property

Absorption AUC: The area under the plot of plasma concentration (AUC) of drug is 122 mcgh/L [3]
Absorption Cmax: The maximum plasma concentration (Cmax) of drug is 119 mcg/L [3]
Clearance: The clearance of drug is 59.6 L/h [4]
Elimination: Approximately 70% of oliceridine is eliminated via the renal route, of which only 0.97-6.75% of an initial dose is recovered unchanged, and the remaining 30% is eliminated in feces [5]
Half-life: The concentration or amount of drug in body reduced by one-half in 1.3 - 3 hours [5]
Metabolism: The drug is metabolized via the hepatic [5]
Vd: The volume of distribution (Vd) of drug is 90-120 L [5]

Chemical Identifiers

Formula: C22H30N2O2S
IUPAC Name: N-[(3-methoxythiophen-2-yl)methyl]-2-[(9R)-9-pyridin-2-yl-6-oxaspiro[4.5]decan-9-yl]ethanamine
Canonical SMILES: COC1=C(SC=C1)CNCC[C@]2(CCOC3(C2)CCCC3)C4=CC=CC=N4
InChI: InChI=1S/C22H30N2O2S/c1-25-18-7-15-27-19(18)16-23-13-10-21(20-6-2-5-12-24-20)11-14-26-22(17-21)8-3-4-9-22/h2,5-7,12,15,23H,3-4,8-11,13-14,16-17H2,1H3/t21-/m1/s1
InChIKey: DMNOVGJWPASQDL-OAQYLSRUSA-N

Cross-matching ID

PubChem CID: 66553195
CAS Number: 1401028-24-7
DrugBank ID: DB14881
TTD ID: D06ENM
INTEDE ID: DR1775
ACDINA ID: D01296

Molecular Interaction Atlas of This Drug

Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 2D6 (CYP2D6)_{Main DME}	DECB0K3	CP2D6_HUMAN	Substrate	[6]

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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 Disease Different from Oliceridine (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Givosiran	DM5PFIJ	Major	Decreased metabolism of Oliceridine caused by Givosiran mediated inhibition of CYP450 enzyme.	Inborn porphyrin/heme metabolism error [5C58]	[17]
Berotralstat	DMWA2DZ	Moderate	Decreased metabolism of Oliceridine caused by Berotralstat mediated inhibition of CYP450 enzyme.	Innate/adaptive immunodeficiency [4A00]	[18]
Selpercatinib	DMZR15V	Major	Increased risk of prolong QT interval by the combination of Oliceridine and Selpercatinib.	Lung cancer [2C25]	[19]
Voxelotor	DMCS6M5	Major	Decreased metabolism of Oliceridine caused by Voxelotor mediated inhibition of CYP450 enzyme.	Sickle-cell disorder [3A51]	[17]
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Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Histidine	E00106	6274	Antioxidant; Buffering agent
Mannitol	E00103	6251	Diluent; Flavoring agent; Lyophilization aid; Plasticizing agent; Tonicity agent
Water	E00035	962	Solvent
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Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Oliceridine 1 mg/ml Injection	1 mg/ml	Injection	Intravenous

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2020
2	A G protein-biased ligand at the -opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine. J Pharmacol Exp Ther. 2013 Mar;344(3):708-17.
3	Soergel DG, Subach RA, Burnham N, Lark MW, James IE, Sadler BM, Skobieranda F, Violin JD, Webster LR: Biased agonism of the mu-opioid receptor by TRV130 increases analgesia and reduces on-target adverse effects versus morphine: A randomized, double-blind, placebo-controlled, crossover study in healthy volunteers. Pain. 2014 Sep;155(9):1829-35. doi: 10.1016/j.pain.2014.06.011. Epub 2014 Jun 19.
4	Fossler MJ, Sadler BM, Farrell C, Burt DA, Pitsiu M, Skobieranda F, Soergel DG: Oliceridine, a Novel G Protein-Biased Ligand at the mu-Opioid Receptor, Demonstrates a Predictable Relationship Between Plasma Concentrations and Pain Relief. II: Simulation of Potential Phase 3 Study Designs Using a Pharmacokinetic/Pharmacodynamic Model. J Clin Pharmacol. 2018 Jun;58(6):762-770. doi: 10.1002/jcph.1075. Epub 2018 Feb 2.
5	FDA Approved Drug Products: Olinvyk (oliceridine) injection
6	First clinical experience with TRV130: pharmacokinetics and pharmacodynamics in healthy volunteers. J Clin Pharmacol. 2014 Mar;54(3):351-7.
7	Inhibitory effects of anticancer drugs on dextromethorphan-O-demethylase activity in human liver microsomes. Cancer Chemother Pharmacol. 1993;32(6):491-5.
8	Effect of genetic polymorphism on the metabolism of endogenous neuroactive substances, progesterone and p-tyramine, catalyzed by CYP2D6. Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):117-23.
9	CYP2D6 polymorphisms and tamoxifen metabolism: clinical relevance. Curr Oncol Rep. 2010 Jan;12(1):7-15.
10	Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies. J Pharm Pharmacol. 2017 Dec;69(12):1762-1772.
11	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
12	Inhibition of cytochrome P450 2D6: structure-activity studies using a series of quinidine and quinine analogues. Chem Res Toxicol. 2003 Apr;16(4):450-9.
13	Effects of propofol on human hepatic microsomal cytochrome P450 activities. Xenobiotica. 1998 Sep;28(9):845-53.
14	Pharmacogenetics of schizophrenia. Am J Med Genet. 2000 Spring;97(1):98-106.
15	Roles of CYP2A6 and CYP2B6 in nicotine C-oxidation by human liver microsomes. Arch Toxicol. 1999 Mar;73(2):65-70.
16	Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82.
17	Gunston GD, Mehta U "Potentially serious drug interactions with grapefruit juice." S Afr Med J 90 (2000): 41. [PMID: 10721388]
18	Product Information. Orladeyo (berotralstat). BioCryst Pharmaceuticals Inc, Durham, NC.
19	Product Information. Olinvyk (oliceridine). Trevena Inc, Chesterbrook, PA.