Details
Stereochemistry | RACEMIC |
Molecular Formula | C27H38N2O4 |
Molecular Weight | 454.6016 |
Optical Activity | ( + / - ) |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=C(OC)C=C(CCN(C)CCCC(C#N)(C(C)C)C2=CC(OC)=C(OC)C=C2)C=C1
InChI
InChIKey=SGTNSNPWRIOYBX-UHFFFAOYSA-N
InChI=1S/C27H38N2O4/c1-20(2)27(19-28,22-10-12-24(31-5)26(18-22)33-7)14-8-15-29(3)16-13-21-9-11-23(30-4)25(17-21)32-6/h9-12,17-18,20H,8,13-16H2,1-7H3
Molecular Formula | C27H38N2O4 |
Molecular Weight | 454.6016 |
Charge | 0 |
Count |
|
Stereochemistry | RACEMIC |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 1 |
E/Z Centers | 0 |
Optical Activity | ( + / - ) |
DescriptionCurator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB00661
Curator's Comment: Description was created based on several sources, including https://www.drugbank.ca/drugs/DB00661
Verapamil is a FDA approved drug used to treat high blood pressure and to control chest pain. Verapamil is an L-type calcium channel blocker that also has antiarrythmic activity. The R-enantiomer is more effective at reducing blood pressure compared to the S-enantiomer. However, the S-enantiomer is 20 times more potent than the R-enantiomer at prolonging the PR interval in treating arrhythmias. Verapamil inhibits voltage-dependent calcium channels. Specifically, its effect on L-type calcium channels in the heart causes a reduction in ionotropy and chronotropy, thuis reducing heart rate and blood pressure. Verapamil's mechanism of effect in cluster headache is thought to be linked to its calcium-channel blocker effect, but which channel subtypes are involved is presently not known.
CNS Activity
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19125880
Curator's Comment: As a lipophilic substance, verapamil easily crosses
the blood–brain barrier. Verapamil is, however, a
substrate for the efflux transporter P-glycoprotein
(P-gp) in the blood–brain barrier. The P-pg restricts
net brain uptake of verapamil by immediately transporting
it out of the brain.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
3.4 µM [IC50] | |||
Target ID: CHEMBL1940 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | CALAN Approved UseCALAN tablets are indicated for the treatment of the following:
Angina
1. Angina at rest including:
— Vasospastic (Prinzmetal’s variant) angina
— Unstable (crescendo, pre-infarction) angina
2. Chronic stable angina (classic effort-associated angina)
Arrhythmias
1. In association with digitalis for the control of ventricular rate at rest and during
stress in patients with chronic atrial flutter and/or atrial fibrillation (see
WARNINGS: Accessory bypass tract)
2. Prophylaxis of repetitive paroxysmal supraventricular tachycardia
Essential hypertension
CALAN is indicated for the treatment of hypertension, to lower blood pressure. Lowering
blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily
strokes and myocardial infarctions. These benefits have been seen in controlled trials of
antihypertensive drugs from a wide variety of pharmacologic classes including this drug. Launch Date3.66336016E11 |
|||
Primary | CALAN Approved UseCALAN tablets are indicated for the treatment of the following:
Angina
1. Angina at rest including:
— Vasospastic (Prinzmetal’s variant) angina
— Unstable (crescendo, pre-infarction) angina
2. Chronic stable angina (classic effort-associated angina)
Arrhythmias
1. In association with digitalis for the control of ventricular rate at rest and during
stress in patients with chronic atrial flutter and/or atrial fibrillation (see
WARNINGS: Accessory bypass tract)
2. Prophylaxis of repetitive paroxysmal supraventricular tachycardia
Essential hypertension
CALAN is indicated for the treatment of hypertension, to lower blood pressure. Lowering
blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily
strokes and myocardial infarctions. These benefits have been seen in controlled trials of
antihypertensive drugs from a wide variety of pharmacologic classes including this drug. Launch Date3.66336016E11 |
|||
Primary | CALAN Approved UseCALAN tablets are indicated for the treatment of the following:
Angina
1. Angina at rest including:
— Vasospastic (Prinzmetal’s variant) angina
— Unstable (crescendo, pre-infarction) angina
2. Chronic stable angina (classic effort-associated angina)
Arrhythmias
1. In association with digitalis for the control of ventricular rate at rest and during
stress in patients with chronic atrial flutter and/or atrial fibrillation (see
WARNINGS: Accessory bypass tract)
2. Prophylaxis of repetitive paroxysmal supraventricular tachycardia
Essential hypertension
CALAN is indicated for the treatment of hypertension, to lower blood pressure. Lowering
blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily
strokes and myocardial infarctions. These benefits have been seen in controlled trials of
antihypertensive drugs from a wide variety of pharmacologic classes including this drug. Launch Date3.66336016E11 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
139.28 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16892180 |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
VERAPAMIL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
367.05 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16892180 |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
VERAPAMIL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
7.15 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/16892180 |
80 mg single, oral dose: 80 mg route of administration: Oral experiment type: SINGLE co-administered: |
VERAPAMIL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
9.9% EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/6209501 |
VERAPAMIL plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/11996015/ Page: 146.0 |
likely | |||
moderate [IC50 23 uM] | ||||
Sources: https://pubmed.ncbi.nlm.nih.gov/11996015/ Page: 99.0 |
weak | |||
yes [IC50 1.23 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Page: 7.0 |
yes | |||
Page: 7.0 |
yes | |||
Page: 7.0 |
yes | |||
Page: 7.0 |
yes | |||
Page: 7.0 |
yes | yes (co-administration study) Comment: Co-administration of multiple doses of 10 mg of verapamil with 80 mg simvastatin resulted in exposure to simvastatin 2.5-fold that following simvastatin alone; Clinically significant interactions have been reported with inhibitors of CYP3A4 (e.g., erythromycin, ritonavir) causing elevation of plasma levels of verapamil while inducers of CYP3A4 (e.g., rifampin) have caused a lowering of plasma levels of verapamil Page: 7.0 |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
[Asystole followed by cardiogenic shock after intravenous injection of verapamil]. | 1975 Mar-Apr |
|
Increase in doxorubicin cytotoxicity by carvedilol inhibition of P-glycoprotein activity. | 1999 Dec 1 |
|
Evidence of sex related differences in the effects of calcium channel blockers on neuroleptic-induced catalepsy in mice. | 1999 Feb |
|
Comparison of intravenous metoprolol, verapamil and diltiazem on the attenuation of haemodynamic changes associated with tracheal extubation. | 1999 Jul |
|
[Verapamil sensitive ventricular tachycardia with myocardial failure in a 2-year-old child]. | 1999 May |
|
P-glycoprotein system as a determinant of drug interactions: the case of digoxin-verapamil. | 1999 Oct |
|
Complete atrioventricular blockade secondary to conventional-release verapamil in a patient on hemodialysis. | 1999 Sep |
|
Sleep attacks and Parkinson's disease treatment. | 2000 Apr 15 |
|
Motor and electrographic response of refractory experimental status epilepticus in rats and effect of calcium channel blockers. | 2000 Feb |
|
Role of the beta(3)-adrenoceptor in urine storage in the rat: comparison between the selective beta(3)-adrenoceptor agonist, CL316, 243, and various smooth muscle relaxants. | 2000 Jun |
|
Transition-state formation in ATPase-negative mutants of human MDR1 protein. | 2000 Oct 5 |
|
Activating transcription factor 2-derived peptides alter resistance of human tumor cell lines to ultraviolet irradiation and chemical treatment. | 2001 Feb |
|
[Treatment of cluster headache]. | 2001 Feb |
|
Pretreatment with potent P-glycoprotein ligands may increase intestinal secretion in rats. | 2001 Feb |
|
Oxidized-LDL enhances coronary vasoconstriction by increasing the activity of protein kinase C isoforms alpha and epsilon. | 2001 Feb |
|
Refractory no-reflow successfully treated with local infusion of high-dose adenosine and verapamil--a case report. | 2001 Feb |
|
Idiopathic sustained left ventricular tachycardia in pediatric patients. | 2001 Feb |
|
Pharmacokinetic interaction of cytochrome P450 3A-related compounds with rhodamine 123, a P-glycoprotein substrate, in rats pretreated with dexamethasone. | 2001 Feb |
|
Ivermectin excretion by isolated functionally intact brain endothelial capillaries. | 2001 Feb |
|
Multidrug resistance protein (MRP) activity in normal mature leukocytes and CD34-positive hematopoietic cells from peripheral blood. | 2001 Feb 2 |
|
Mechanisms of the increased pressor response to vasopressors in the mesenteric bed of nitric oxide-deficient hypertensive rats. | 2001 Feb 2 |
|
Cardiovascular action of a cardioselective Ca(2+)channel blocker AH-1058 in conscious dogs assessed by telemetry. | 2001 Feb 9 |
|
Identification of an organic anion transport system in the human colon carcinoma cell line HT29 clone 19A. | 2001 Jan |
|
Prevention of cardiomyopathy in mouse models lacking the smooth muscle sarcoglycan-sarcospan complex. | 2001 Jan |
|
Sarcoglycan, the heart, and skeletal muscles: new treatment, old drug? | 2001 Jan |
|
Left ventricular midwall function improves with antihypertensive therapy and regression of left ventricular hypertrophy in patients with asymptomatic hypertension. | 2001 Jan 1 |
|
Behavioural and anti-psychotic effects of Ca2+ channel blockers in rhesus monkey. | 2001 Jan 26 |
|
Cardiogenic shock following a single therapeutic oral dose of verapamil. | 2001 Jan-Feb |
|
Verapamil SR and trandolapril combination therapy is safe and effective in hypertensive patients with metabolic disorders. | 2001 Jan-Feb |
|
PSA-specific and non-PSA-specific conversion of a PSA-targeted peptide conjugate of doxorubicin to its active metabolites. | 2001 Mar |
|
Correlation between steady-state ATP hydrolysis and vanadate-induced ADP trapping in Human P-glycoprotein. Evidence for ADP release as the rate-limiting step in the catalytic cycle and its modulation by substrates. | 2001 Mar 23 |
|
The effect of cardiac arrest on the blood-testis barrier to albumin, tumor necrosis factor-alpha, pituitary adenylate cyclase activating polypeptide, sucrose, and verapamil in the mouse. | 2001 Mar-Apr |
Sample Use Guides
Angina: Clinical trials show that the usual dose is 80 mg to 120 mg three times a day.
However, 40 mg three times a day may be warranted in patients who may have an
increased response to verapamil (eg, decreased hepatic function, elderly, etc). Upward
titration should be based on therapeutic efficacy and safety evaluated approximately eight
hours after dosing. Dosage may be increased at daily (eg, patients with unstable angina)
or weekly intervals until optimum clinical response is obtained.
Arrhythmias: The dosage in digitalized patients with chronic atrial fibrillation (see
PRECAUTIONS) ranges from 240 to 320 mg/day in divided (t.i.d. or q.i.d.) doses. The
dosage for prophylaxis of PSVT (non-digitalized patients) ranges from 240 to
480 mg/day in divided (t.i.d. or q.i.d.) doses. In general, maximum effects for any given
dosage will be apparent during the first 48 hours of therapy.
Essential hypertension: Dose should be individualized by titration. The usual initial
monotherapy dose in clinical trials was 80 mg three times a day (240 mg/day). Daily
dosages of 360 and 480 mg have been used but there is no evidence that dosages beyond
360 mg provided added effect. Consideration should be given to beginning titration at
40 mg three times per day in patients who might respond to lower doses, such as the
elderly or people of small stature. The antihypertensive effects of CALAN are evident
within the first week of therapy. Upward titration should be based on therapeutic
efficacy, assessed at the end of the dosing interval.
Route of Administration:
Other
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/27763693
Blockade of L-type calcium channels by verapamil (50 um) prevented a Norgestrel-induced calcium influx in stressed 661W photoreceptor-like cells.
Substance Class |
Chemical
Created
by
admin
on
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Record UNII |
CJ0O37KU29
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Record Status |
Validated (UNII)
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NDF-RT |
N0000175566
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WHO-VATC |
QC09BB10
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QC08DA01
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WHO-ATC |
C08DA51
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NCI_THESAURUS |
C333
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WHO-ESSENTIAL MEDICINES LIST |
12.2
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WHO-ESSENTIAL MEDICINES LIST |
12.1
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WHO-VATC |
QC08DA51
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NDF-RT |
N0000000069
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WHO-ATC |
C09BB10
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LIVERTOX |
NBK548362
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WHO-ATC |
C08DA01
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200-145-1
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9948
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2520
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2406
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CJ0O37KU29
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2122
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N0000182141
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PRIMARY | Cytochrome P450 3A4 Inhibitors [MoA] | ||
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11170
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100000079099
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52-53-9
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VERAPAMIL
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Verapamil
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DB00661
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D014700
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2815
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N0000185503
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PRIMARY | P-Glycoprotein Inhibitors [MoA] | ||
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C928
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CJ0O37KU29
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M11414
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PRIMARY | Merck Index | ||
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DTXSID9041152
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SUB00038MIG
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CHEMBL6966
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N0000190114
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PRIMARY | Cytochrome P450 3A Inhibitors [MoA] |
Related Record | Type | Details | ||
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BINDER->LIGAND |
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METABOLIC ENZYME -> INHIBITOR | |||
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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METABOLIC ENZYME -> INHIBITOR |
IC50
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE | |||
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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SALT/SOLVATE -> PARENT | |||
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TRANSPORTER -> INHIBITOR |
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METABOLIC ENZYME -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR |
Related Record | Type | Details | ||
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METABOLITE -> PARENT |
22% 0f dose
MAJOR
URINE
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METABOLITE ACTIVE -> PARENT | |||
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METABOLITE ACTIVE -> PARENT |
MAJOR
PLASMA
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METABOLITE -> PARENT |
3-4% of dose
MINOR
URINE
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METABOLITE -> PARENT |
3-4% of dose
MINOR
URINE
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METABOLITE -> PARENT |
7% of dose
URINE
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METABOLITE -> PARENT |
6% of dose
MINOR
URINE
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METABOLITE ACTIVE -> PARENT |
6% of dose
MINOR
URINE
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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Volume of Distribution | PHARMACOKINETIC |
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Populations PHARMACOKINETIC |
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Duration of Action | PHARMACOKINETIC |
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Volume of Distribution | PHARMACOKINETIC |
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Populations PHARMACOKINETIC |
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Duration of Action | PHARMACOKINETIC |
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