U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C29H53NO5
Molecular Weight 495.7359
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ORLISTAT

SMILES

CCCCCCCCCCC[C@@]([H])(C[C@@]1([H])[C@]([H])(CCCCCC)C(=O)O1)OC(=O)[C@]([H])(CC(C)C)N=CO

InChI

InChIKey=AHLBNYSZXLDEJQ-FWEHEUNISA-N
InChI=1S/C29H53NO5/c1-5-7-9-11-12-13-14-15-16-18-24(34-29(33)26(30-22-31)20-23(3)4)21-27-25(28(32)35-27)19-17-10-8-6-2/h22-27H,5-21H2,1-4H3,(H,30,31)/t24-,25-,26-,27-/m0/s1

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including http://www.fda.gov/downloads/UCM205349.pdf https://www.ncbi.nlm.nih.gov/pubmed/9225172 https://www.ncbi.nlm.nih.gov/pubmed/16956313

Orlistat or tetrahydrolipstatin (Xenical, Hoffmann-La Roche) is a saturated derivative of lipstatin originally isolated from Streptomyces toxytricini. Orlistat (Xenical, Hoffmann-La Roche) is a powerful inhibitor of gastrointestinal lipase and as such, reduces fat absorption. Orlistat acts by binding covalently to the serine residue of the active site of gastric and pancreatic lipases. When administered with fat-containing foods, orlistat partially inhibits hydrolysis of triglycerides, thus reducing the subsequent absorption of monoaclglycerides and free fatty acids. Unlike other weight-reducing drugs it is minimally absorbed and has no effects in the CNS. Xenical is indicated for obesity management including weight loss and weight maintenance when used in conjunction witha reduced-calorie diet. XENICAL is also indicated to reduce the risk for weight regain after prior weight loss. XENICAL is indicated for obese patients with an initial body mass index (BMI) ≥ 30 kg/m2 or ≥ 27 kg/m2 in the presence of other risk factors (eg, hypertension, diabetes, dyslipidemia). In addition to its well established efficacy in achieving modest weight loss, orlistat has been shown to improve glycaemic parameters in obese adults with type 2 diabetes mellitus as well as some features of the metabolic syndrome.

CNS Activity

Curator's Comment:: Orlistat is minimally absorbed and has no effects in the CNS

Originator

Curator's Comment:: # Hoffmann-La Roche & Co., Ltd.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
XENICAL

Approved Use

XENICAL orlistat capsule is indicated for obesity management including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet. XENICAL is also indicated to reduce the risk for weight regain after prior weight loss. XENICAL is indicated for obese patients with an initial body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 in the presence of other risk factors (eg, hypertension, diabetes, dyslipidemia).

Launch Date

9.2482562E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
150 ng × eq/mL
360 mg single, oral
dose: 360 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORLISTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
907 ng × eq × h/mL
360 mg single, oral
dose: 360 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
ORLISTAT plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.5 h
ORLISTAT plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
1%
ORLISTAT plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
5160 mg single, oral
Overdose
Dose: 5160 mg
Route: oral
Route: single
Dose: 5160 mg
Sources:
healthy, 28 months
n = 1
Health Status: healthy
Age Group: 28 months
Sex: F
Population Size: 1
Sources:
30 mg 1 times / day steady, oral
Dose: 30 mg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg, 1 times / day
Sources:
healthy, 51 years (range: 30-65 year)
n = 33
Health Status: healthy
Age Group: 51 years (range: 30-65 year)
Sex: M+F
Population Size: 33
Sources:
Disc. AE: Fatigue...
AEs leading to
discontinuation/dose reduction:
Fatigue (1 patient)
Sources:
120 mg 3 times / day steady, oral
Recommended
Dose: 120 mg, 3 times / day
Route: oral
Route: steady
Dose: 120 mg, 3 times / day
Sources:
healthy, 52 years (range: 30-65 year)
n = 35
Health Status: healthy
Age Group: 52 years (range: 30-65 year)
Sex: M+F
Population Size: 35
Sources:
Disc. AE: Rectal oily spotting, Flatus...
AEs leading to
discontinuation/dose reduction:
Rectal oily spotting (1 patient)
Flatus (1 patient)
Abdominal pain (1 patient)
Painful defaecation (1 patient)
Sources:
180 mg 1 times / day steady, oral
Dose: 180 mg, 1 times / day
Route: oral
Route: steady
Dose: 180 mg, 1 times / day
Sources:
healthy, 53 years (range: 30-65 year)
n = 35
Health Status: healthy
Age Group: 53 years (range: 30-65 year)
Sex: M+F
Population Size: 35
Sources:
Disc. AE: Loose stools, Myocardial infarction...
AEs leading to
discontinuation/dose reduction:
Loose stools (2 patients)
Myocardial infarction (1 patient)
Sources:
60 mg 3 times / day steady, oral
Recommended
Dose: 60 mg, 3 times / day
Route: oral
Route: steady
Dose: 60 mg, 3 times / day
Sources:
healthy, 54 years
n = 1
Health Status: healthy
Age Group: 54 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Fatigue, Weakness generalized...
AEs leading to
discontinuation/dose reduction:
Fatigue
Weakness generalized
Nausea
Jaundice
Pruritus
Hepatic failure
Sources:
90 mg 1 times / day steady, oral
Dose: 90 mg, 1 times / day
Route: oral
Route: steady
Dose: 90 mg, 1 times / day
Sources:
healthy, 55 years (range: 30-65 year)
n = 33
Health Status: healthy
Age Group: 55 years (range: 30-65 year)
Sex: M+F
Population Size: 33
Sources:
Disc. AE: Loose stools...
AEs leading to
discontinuation/dose reduction:
Loose stools (2 patients)
Sources:
120 mg 3 times / day steady, oral
Recommended
Dose: 120 mg, 3 times / day
Route: oral
Route: steady
Dose: 120 mg, 3 times / day
Sources:
healthy, adult
n = 1913
Health Status: healthy
Age Group: adult
Population Size: 1913
Sources:
Disc. AE: Gastrointestinal symptom NOS...
AEs leading to
discontinuation/dose reduction:
Gastrointestinal symptom NOS (8.8%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Fatigue 1 patient
Disc. AE
30 mg 1 times / day steady, oral
Dose: 30 mg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg, 1 times / day
Sources:
healthy, 51 years (range: 30-65 year)
n = 33
Health Status: healthy
Age Group: 51 years (range: 30-65 year)
Sex: M+F
Population Size: 33
Sources:
Abdominal pain 1 patient
Disc. AE
120 mg 3 times / day steady, oral
Recommended
Dose: 120 mg, 3 times / day
Route: oral
Route: steady
Dose: 120 mg, 3 times / day
Sources:
healthy, 52 years (range: 30-65 year)
n = 35
Health Status: healthy
Age Group: 52 years (range: 30-65 year)
Sex: M+F
Population Size: 35
Sources:
Flatus 1 patient
Disc. AE
120 mg 3 times / day steady, oral
Recommended
Dose: 120 mg, 3 times / day
Route: oral
Route: steady
Dose: 120 mg, 3 times / day
Sources:
healthy, 52 years (range: 30-65 year)
n = 35
Health Status: healthy
Age Group: 52 years (range: 30-65 year)
Sex: M+F
Population Size: 35
Sources:
Painful defaecation 1 patient
Disc. AE
120 mg 3 times / day steady, oral
Recommended
Dose: 120 mg, 3 times / day
Route: oral
Route: steady
Dose: 120 mg, 3 times / day
Sources:
healthy, 52 years (range: 30-65 year)
n = 35
Health Status: healthy
Age Group: 52 years (range: 30-65 year)
Sex: M+F
Population Size: 35
Sources:
Rectal oily spotting 1 patient
Disc. AE
120 mg 3 times / day steady, oral
Recommended
Dose: 120 mg, 3 times / day
Route: oral
Route: steady
Dose: 120 mg, 3 times / day
Sources:
healthy, 52 years (range: 30-65 year)
n = 35
Health Status: healthy
Age Group: 52 years (range: 30-65 year)
Sex: M+F
Population Size: 35
Sources:
Myocardial infarction 1 patient
Disc. AE
180 mg 1 times / day steady, oral
Dose: 180 mg, 1 times / day
Route: oral
Route: steady
Dose: 180 mg, 1 times / day
Sources:
healthy, 53 years (range: 30-65 year)
n = 35
Health Status: healthy
Age Group: 53 years (range: 30-65 year)
Sex: M+F
Population Size: 35
Sources:
Loose stools 2 patients
Disc. AE
180 mg 1 times / day steady, oral
Dose: 180 mg, 1 times / day
Route: oral
Route: steady
Dose: 180 mg, 1 times / day
Sources:
healthy, 53 years (range: 30-65 year)
n = 35
Health Status: healthy
Age Group: 53 years (range: 30-65 year)
Sex: M+F
Population Size: 35
Sources:
Fatigue Disc. AE
60 mg 3 times / day steady, oral
Recommended
Dose: 60 mg, 3 times / day
Route: oral
Route: steady
Dose: 60 mg, 3 times / day
Sources:
healthy, 54 years
n = 1
Health Status: healthy
Age Group: 54 years
Sex: F
Population Size: 1
Sources:
Hepatic failure Disc. AE
60 mg 3 times / day steady, oral
Recommended
Dose: 60 mg, 3 times / day
Route: oral
Route: steady
Dose: 60 mg, 3 times / day
Sources:
healthy, 54 years
n = 1
Health Status: healthy
Age Group: 54 years
Sex: F
Population Size: 1
Sources:
Jaundice Disc. AE
60 mg 3 times / day steady, oral
Recommended
Dose: 60 mg, 3 times / day
Route: oral
Route: steady
Dose: 60 mg, 3 times / day
Sources:
healthy, 54 years
n = 1
Health Status: healthy
Age Group: 54 years
Sex: F
Population Size: 1
Sources:
Nausea Disc. AE
60 mg 3 times / day steady, oral
Recommended
Dose: 60 mg, 3 times / day
Route: oral
Route: steady
Dose: 60 mg, 3 times / day
Sources:
healthy, 54 years
n = 1
Health Status: healthy
Age Group: 54 years
Sex: F
Population Size: 1
Sources:
Pruritus Disc. AE
60 mg 3 times / day steady, oral
Recommended
Dose: 60 mg, 3 times / day
Route: oral
Route: steady
Dose: 60 mg, 3 times / day
Sources:
healthy, 54 years
n = 1
Health Status: healthy
Age Group: 54 years
Sex: F
Population Size: 1
Sources:
Weakness generalized Disc. AE
60 mg 3 times / day steady, oral
Recommended
Dose: 60 mg, 3 times / day
Route: oral
Route: steady
Dose: 60 mg, 3 times / day
Sources:
healthy, 54 years
n = 1
Health Status: healthy
Age Group: 54 years
Sex: F
Population Size: 1
Sources:
Loose stools 2 patients
Disc. AE
90 mg 1 times / day steady, oral
Dose: 90 mg, 1 times / day
Route: oral
Route: steady
Dose: 90 mg, 1 times / day
Sources:
healthy, 55 years (range: 30-65 year)
n = 33
Health Status: healthy
Age Group: 55 years (range: 30-65 year)
Sex: M+F
Population Size: 33
Sources:
Gastrointestinal symptom NOS 8.8%
Disc. AE
120 mg 3 times / day steady, oral
Recommended
Dose: 120 mg, 3 times / day
Route: oral
Route: steady
Dose: 120 mg, 3 times / day
Sources:
healthy, adult
n = 1913
Health Status: healthy
Age Group: adult
Population Size: 1913
Sources:
PubMed

PubMed

TitleDatePubMed
Orlistat.
2000 Mar-Apr
Orlistat: in the prevention and treatment of type 2 diabetes mellitus.
2001
Evidence for specific ceramidase present in the intestinal contents of rats and humans.
2001 Aug
Primary care diabetes. What options are there?
2001 Dec
Bulimia nervosa and misuse of orlistat: two case reports.
2001 Dec
[Changes in lipid profile and paraoxonase activity in obese patients as a result of orlistat treatment].
2001 Dec 16
Online prescriptions of pharmaceuticals: where is the evidence for harm or for benefit? A call for papers--and for reflection.
2001 Jan-Mar
Incorrect use and limited weight reduction of orlistat (Xenical) in clinical practice. A cohort study.
2001 Jul
Current methods used for defining, measuring, and treating obesity.
2001 Nov
The effects of orlistat on weight and on serum lipids in obese patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled, multicentre study.
2001 Nov
[Inhibitors of absorption as anti-obesity drugs].
2001 Nov
Interaction between orlistat and antihypertensive drugs.
2001 Nov
Lipoprotein lipase mediates an increase in selective uptake of HDL-associated cholesteryl esters by cells in culture independent of scavenger receptor BI.
2001 Nov
Role of nonesterified fatty acids in necrotizing pancreatitis: an in vivo experimental study in rats.
2001 Nov
[Application for exemption concerning Xenical was refused without explanation].
2001 Nov 7
Drug treatment of obesity.
2001 Oct
Orlistat inhibits dietary cholesterol absorption.
2001 Oct
Principles for enhanced recruitment of subjects in a large clinical trial. the XENDOS (XENical in the prevention of Diabetes in Obese Subjects) study experience.
2001 Oct
[Therapy of obesity. Setting realistic goals].
2001 Oct 18
About orlistat.
2001 Sep
Ezetimibe selectively inhibits intestinal cholesterol absorption in rodents in the presence and absence of exocrine pancreatic function.
2001 Sep
Weighing the options in the pharmacotherapy of obesity.
2001 Sep
Pathophysiology and treatment of the dyslipidemia of insulin resistance.
2001 Sep
[Weight reduction. Antiobesity drug treatment in type-2 diabetics].
2002
[Six-month xenical (orlistat) therapy of patients with stable angina pectoris concomitant with obesity and hyperlipidemia].
2002
[Orlistat. A treatment of limited value for obese persons].
2002 Apr
Roche turns to DM to boost patient compliance with its weight loss drug.
2002 Apr
The cerebrospinal fluid/serum leptin ratio during pharmacological therapy for obesity.
2002 Apr
Orlistat: its current status as an anti-obesity drug.
2002 Apr 12
Biosynthetic precursors of the lipase inhibitor lipstatin.
2002 Apr 5
Effects of lipoprotein lipase on uptake and transcytosis of low density lipoprotein (LDL) and LDL-associated alpha-tocopherol in a porcine in vitro blood-brain barrier model.
2002 Aug 9
Orlistat: a second look. At best, a minor adjunct to dietary measures.
2002 Feb
Impact of orlistat therapy on weight reduction in morbidly obese patients after implantation of the Swedish adjustable gastric band.
2002 Feb
A health economic model to assess the long-term effects and cost-effectiveness of orlistat in obese type 2 diabetic patients.
2002 Feb
The effect of orlistat on plasma levels of psychotropic drugs in patients with long-term psychopharmacotherapy.
2002 Feb
Are soft tissue composition of bone and non-bone pixels in spinal bone mineral measurements by DXA similar? Impact of weight loss.
2002 Jan
Minor long-term changes in weight have beneficial effects on insulin sensitivity and beta-cell function in obese subjects.
2002 Jan
Evaluation of the safety and efficacy of sibutramine, orlistat and metformin in the treatment of obesity.
2002 Jan
Usefulness of Orlistat in the treatment of severe hypertriglyceridemia.
2002 Jan 15
[Treatment in the community health centers in accordance with recommendations of the Medical Products Agency. Unsatisfactory weight reduction with orlistat].
2002 Jan 31
[Are drugs necessary in the treatment of obesity?].
2002 Jan-Feb
Constipation, polyuria, polydipsia, and edema associated with orlistat.
2002 Jul-Aug
Combining behavioral and pharmacological treatments for obesity.
2002 Jun
Additive gastrointestinal effects with concomitant use of olestra and orlistat.
2002 Jun
Can drugs help you lose weight?
2002 Mar
Orlistat misuse in bulimia nervosa.
2002 Mar
[Anti-obesity drugs: sibutramine and orlistat].
2002 Mar 30
Serine and threonine beta-lactones: a new class of hepatitis A virus 3C cysteine proteinase inhibitors.
2002 Mar 8
Obesity in transplant patients: case report showing interference of orlistat with absorption of cyclosporine and review of literature.
2002 Mar-Apr
Orlistat in the treatment of Type 2 diabetes mellitus.
2002 May
Patents

Sample Use Guides

In Vivo Use Guide
The recommended dose of XENICAL (orlistat capsule) is one 120-mg capsule three times a day with each main meal containing fat (during or up to 1 hour after the meal).
Route of Administration: Oral
Orlistat inhibited cell proliferation by 61 % in ECC-1 cells and 57 % in KLE cells at a dose of 500 μM
Name Type Language
ORLISTAT
EMA EPAR   HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
ORLISTAT [USP-RS]
Common Name English
ORLISTAT [USP MONOGRAPH]
Common Name English
ORLISTAT [MART.]
Common Name English
RO-180647-002
Code English
XENICAL
Brand Name English
ORLISTAT [INN]
Common Name English
RO-18-0647/002
Code English
RO 18-0647/002
Code English
L-LEUCINE, N-FORMYL-, 1-((3-HEXYL-4-OXO-2-OXETANYL)METHYL)DODECYL ESTER, (2S-(2.ALPHA.(R*),3.BETA.))-
Common Name English
ORLISTAT [JAN]
Common Name English
ALLI
Brand Name English
ORLISTAT [USAN]
Common Name English
ORLISTAT [VANDF]
Common Name English
N-FORMYL-L-LEUCINE, ESTER WITH (3S,4S)-3-HEXYL-4-((2S)-2-HYDROXYTRIDECYL)-2-OXETANONE
Common Name English
NSC-758881
Code English
ORLISTAT [ORANGE BOOK]
Common Name English
ORLISTAT [HSDB]
Common Name English
RO-180647002
Code English
ORLISTAT [EMA EPAR]
Common Name English
ORLISTAT [WHO-DD]
Common Name English
ORLISTAT [MI]
Common Name English
Classification Tree Code System Code
NDF-RT N0000009916
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
WHO-ATC A08AB01
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
EMA ASSESSMENT REPORTS ALLI (AUTHORIZED: OBESITY)
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
NCI_THESAURUS C29715
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
EMA ASSESSMENT REPORTS XENICAL (AUTHORIZED: OBESITY)
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
NDF-RT N0000175591
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
WHO-VATC QA08AB01
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
LIVERTOX 714
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
Code System Code Type Description
HSDB
7556
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY
DRUG CENTRAL
1996
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY
NCI_THESAURUS
C29303
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY
INN
6318
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY
USP_CATALOG
1478800
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY USP-RS
EVMPD
SUB09460MIG
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY
PUBCHEM
3034010
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY
ChEMBL
CHEMBL175247
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY
WIKIPEDIA
ORLISTAT
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY
IUPHAR
5277
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY
MESH
C055122
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY
EPA CompTox
96829-58-2
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY
RXCUI
37925
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY RxNorm
MERCK INDEX
M8234
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY Merck Index
FDA UNII
95M8R751W8
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY
CAS
96829-58-2
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY
DRUG BANK
DB01083
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY
LACTMED
Orlistat
Created by admin on Fri Jun 25 22:10:20 UTC 2021 , Edited by admin on Fri Jun 25 22:10:20 UTC 2021
PRIMARY