Details of the Drug

General Information of Drug (ID: DMJH792)

Drug Name
Pitavastatin
Synonyms
Pitavastatin; Itavastatin; Livalo; NK 104; Pitavastatin [INN]; Pitavastatin calcium; UNII-M5681Q5F9P; NK-104; C25H24FNO4; M5681Q5F9P; Zypitamag; Flovas; (3R,5S,6E)-7-(2-Cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl)-3,5-dihydroxyhept-6-enoic acid; P 872441; P-872441; (3R,5S,6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoic acid; ( )-(3R,5S,6E)-7-(2-Cyclopropyl-4-(4-fluorophenyl)-3-quinolyl)-3,5-dihydroxy-6-heptenoic acid; NK 104 (acid); Pitavastatin calcium (JAN)
Indication
Disease Entry ICD 11 Status REF
Hypercholesterolaemia 5C80.0 Approved [1]
Hyperlipidemia, familial combined, LPL related N.A. Approved [1]
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski):
0		 Molecular Weight 421.5
Logarithm of the Partition Coefficient Not Available
Rotatable Bond Count 8
Hydrogen Bond Donor Count 3
Hydrogen Bond Acceptor Count 6
ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 1 h []
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 4: low solubility and low permeability [2]
Clearance
The apparent oral clearance of drug is 43.4 L/h [3]
Elimination
A mean of 15% of radioactivity of orally administered, single 32 mg 14C-labeled pitavastatin dose was excreted in urine, whereas a mean of 79% of the dose was excreted in feces within 7 days []
Half-life
The concentration or amount of drug in body reduced by one-half in 12 hours []
Metabolism
The drug is metabolized via the liver uridine 5'-diphosphate glucuronosyltransferase (UGT) with subsequent formation of pitavastatin lactone []
Unbound Fraction
The unbound fraction of drug in plasma is 0.005% [4]
Vd
The volume of distribution (Vd) of drug is 148 L []
Chemical Identifiers
Formula
C25H24FNO4
IUPAC Name
(E,3R,5S)-7-[2-cyclopropyl-4-(4-fluorophenyl)quinolin-3-yl]-3,5-dihydroxyhept-6-enoic acid
Canonical SMILES
C1CC1C2=NC3=CC=CC=C3C(=C2C=CC(CC(CC(=O)O)O)O)C4=CC=C(C=C4)F
InChI
InChI=1S/C25H24FNO4/c26-17-9-7-15(8-10-17)24-20-3-1-2-4-22(20)27-25(16-5-6-16)21(24)12-11-18(28)13-19(29)14-23(30)31/h1-4,7-12,16,18-19,28-29H,5-6,13-14H2,(H,30,31)/b12-11+/t18-,19-/m1/s1
InChIKey
VGYFMXBACGZSIL-MCBHFWOFSA-N
Cross-matching ID
PubChem CID
5282452
ChEBI ID
CHEBI:32020
CAS Number
147511-69-1
DrugBank ID
DB08860
VARIDT ID
DR01545
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Transporter (DTP)
DTP Name DTP ID UniProt ID MOA REF
Multidrug resistance-associated protein 2 (ABCC2) DTFI42L MRP2_HUMAN Substrate [5]
Organic anion transporting polypeptide 2B1 (SLCO2B1) DTPFTEQ SO2B1_HUMAN Substrate [6]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [7]
Breast cancer resistance protein (ABCG2) DTI7UX6 ABCG2_HUMAN Substrate [8]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [9]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [10]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
ATP-binding cassette sub-family C member 2 (ABCC2) OTJSIGV5 MRP2_HUMAN Regulation of Drug Effects [5]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Regulation of Drug Effects [5]
Bcl-2-binding component 3, isoforms 3/4 (BBC3) OTUAXDAY BBC3B_HUMAN Gene/Protein Processing [11]
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Gene/Protein Processing [12]
Broad substrate specificity ATP-binding cassette transporter ABCG2 (ABCG2) OTW8V2V1 ABCG2_HUMAN Regulation of Drug Effects [5]
Cyclic AMP-dependent transcription factor ATF-4 (ATF4) OTRFV19J ATF4_HUMAN Gene/Protein Processing [11]
Peroxisome proliferator-activated receptor alpha (PPARA) OTK095PP PPARA_HUMAN Gene/Protein Processing [13]
Peroxisome proliferator-activated receptor delta (PPARD) OTI4WTOP PPARD_HUMAN Gene/Protein Processing [13]
Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1) OTXEE550 APR_HUMAN Gene/Protein Processing [11]
Phospholipid-transporting ATPase ABCA1 (ABCA1) OT94G6BQ ABCA1_HUMAN Gene/Protein Processing [13]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

References

1 Pitavastatin FDA Label
2 BDDCS predictions, self-correcting aspects of BDDCS assignments, BDDCS assignment corrections, and classification for more than 175 additional drugs
3 Hoy SM: Pitavastatin: A Review in Hypercholesterolemia. Am J Cardiovasc Drugs. 2017 Apr;17(2):157-168. doi: 10.1007/s40256-017-0213-8.
4 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
5 Involvement of BCRP (ABCG2) in the biliary excretion of pitavastatin. Mol Pharmacol. 2005 Sep;68(3):800-7.
6 Intestinal absorption of HMG-CoA reductase inhibitor pitavastatin mediated by organic anion transporting polypeptide and P-glycoprotein/multidrug resistance 1. Drug Metab Pharmacokinet. 2011;26(2):171-9.
7 Transporter-mediated influx and efflux mechanisms of pitavastatin, a new inhibitor of HMG-CoA reductase. J Pharm Pharmacol. 2005 Oct;57(10):1305-11.
8 ABCG2: a perspective. Adv Drug Deliv Rev. 2009 Jan 31;61(1):3-13.
9 Prediction of the in vivo OATP1B1-mediated drug-drug interaction potential of an investigational drug against a range of statins. Eur J Pharm Sci. 2012 Aug 30;47(1):244-55.
10 Impact of OATP transporters on pharmacokinetics. Br J Pharmacol. 2009 Oct;158(3):693-705.
11 Statin-induced Mitochondrial Priming Sensitizes Multiple Myeloma Cells to BCL2 and MCL-1 Inhibitors. Cancer Res Commun. 2023 Dec 8;3(12):2497-2509. doi: 10.1158/2767-9764.CRC-23-0350.
12 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
13 Regulation mechanism of ABCA1 expression by statins in hepatocytes. Eur J Pharmacol. 2011 Jul 15;662(1-3):9-14. doi: 10.1016/j.ejphar.2011.04.043. Epub 2011 May 1.