DESFESOTERODINE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C22H31NO2
Molecular Weight	341.487
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)N(CC[C@H](C1=CC=CC=C1)C2=CC(CO)=CC=C2O)C(C)C

InChI

InChIKey=DUXZAXCGJSBGDW-HXUWFJFHSA-N

InChI=1S/C22H31NO2/c1-16(2)23(17(3)4)13-12-20(19-8-6-5-7-9-19)21-14-18(15-24)10-11-22(21)25/h5-11,14,16-17,20,24-25H,12-13,15H2,1-4H3/t20-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C22H31NO2
Molecular Weight	341.487
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19835561 | DOI: 10.1002/(SICI)1520-6777(1996)15:4<249::AID-NAU1>3.0.CO;2-F | https://www.ncbi.nlm.nih.gov/pubmed/9353847https://www.ncbi.nlm.nih.gov/pubmed/19835561
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18279452

Fesoterodine (trade name Toviaz) is a prodrug of 5-hydroxymethyl tolterodine, which is also the active metabolite of tolterodine. Fesoterodine and its active metabolites are nonsubtype selective, competitive antagonists of human muscarinic receptors, but 5-hydroxymethyl tolterodine has greater potency than the parent compound. A prodrug approach was necessary for systemic bioavailability of 5-hydroxymethyl tolterodine after oral administration. Fesoterodine was originated by Schwarz Pharma (later a subsidiary of UCB) and is being developed by Pfizer for the treatment of overactive bladder and urinary urge incontinence. The agent is launched in several countries for the treatment of overactive bladder, including the US, Japan, Canada, Europe and Asia.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Muscarinic acetylcholine receptor M1 168 Target ID: CHEMBL216 Sources: DOI: 10.1002/(SICI)1520-6777(1996)15:4<249::AID-NAU1>3.0.CO;2-F	Antagonist 2760	2.3 nM [Ki]
Muscarinic acetylcholine receptor M2 120 Target ID: CHEMBL211 Sources: DOI: 10.1002/(SICI)1520-6777(1996)15:4<249::AID-NAU1>3.0.CO;2-F	Antagonist 2760	2.0 nM [Ki]
Muscarinic acetylcholine receptor M3 158 Target ID: CHEMBL245 Sources: DOI: 10.1002/(SICI)1520-6777(1996)15:4<249::AID-NAU1>3.0.CO;2-F	Antagonist 2760	2.5 nM [Ki]
Muscarinic acetylcholine receptor M4 85 Target ID: CHEMBL1821 Sources: DOI: 10.1002/(SICI)1520-6777(1996)15:4<249::AID-NAU1>3.0.CO;2-F	Antagonist 2760	2.8 nM [Ki]
Muscarinic acetylcholine receptor M5 61 Target ID: CHEMBL2035 Sources: DOI: 10.1002/(SICI)1520-6777(1996)15:4<249::AID-NAU1>3.0.CO;2-F	Antagonist 2760	2.9 nM [Ki]
Muscarinic acetylcholine receptor M1 168 Target ID: CHEMBL216 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23497983 \| https://www.ncbi.nlm.nih.gov/pubmed/18279452	Antagonist 2760	8.0 null [pKi]
Muscarinic acetylcholine receptor M2 120 Target ID: CHEMBL211 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23497983 \| https://www.ncbi.nlm.nih.gov/pubmed/18279452	Antagonist 2760	7.7 null [pKi]
Muscarinic acetylcholine receptor M3 158 Target ID: CHEMBL245 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23497983 \| https://www.ncbi.nlm.nih.gov/pubmed/18279452	Antagonist 2760	7.4 null [pKi]
Muscarinic acetylcholine receptor M4 85 Target ID: CHEMBL1821 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23497983 \| https://www.ncbi.nlm.nih.gov/pubmed/18279452	Antagonist 2760	7.3 null [pKi]
Muscarinic acetylcholine receptor M5 61 Target ID: CHEMBL2035 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23497983 \| https://www.ncbi.nlm.nih.gov/pubmed/18279452	Antagonist 2760	7.5 null [pKi]

Conditions

Condition	Modality	Highest Phase	Product
Urinary incontinence 14 Sources: DOI: 10.1002/(SICI)1520-6777(1996)15:4<249::AID-NAU1>3.0.CO;2-F https://www.ncbi.nlm.nih.gov/pubmed/9353847	Primary	Preclinical	Unknown Approved Use Unknown
Partial urethral obstruction 5 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19888972 https://www.ncbi.nlm.nih.gov/pubmed/20639056	Primary	Preclinical	Unknown Approved Use Unknown
Overactive bladder 38 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf	Palliative	Approved 8360	TOVIAZ Approved Use Toviaz is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. Launch Date 1.22532476E12
Overactive bladder 38 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022030lbl.pdf	Primary	Approved 8360	TOVIAZ Approved Use Toviaz® is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. Toviaz is a muscarinic antagonist indicated for the treatment of overactive bladder with symptoms of urge urinary incontinence, urgency, and frequency. Launch Date 1.22541126E12

C_max

Value	Dose	Co-administered	Analyte	Population
1.89 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		5-HYDROXYMETHYL TOLTERODINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
7.31 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		5-HYDROXYMETHYL TOLTERODINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
50% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf	4 mg single, oral dose: 4 mg route of administration: Oral experiment type: SINGLE co-administered:		5-HYDROXYMETHYL TOLTERODINE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
8 mg 1 times / day steady, oral (max) Dose: 8 mg, 1 times / day Route: oral Route: steady Dose: 8 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00928070	unhealthy, adult n = 281 Health Status: unhealthy Condition: Overactive Bladder Age Group: adult Population Size: 281 Sources: https://clinicaltrials.gov/ct2/show/NCT00928070	Other AEs: Coronary artery occlusion, Influenza... Other AEs: Coronary artery occlusion (serious, 1 patient) Influenza (serious, 1 patient) Urosepsis (serious, 1 patient) Fall (serious, 1 patient) Femur fracture (serious, 1 patient) Haemarthrosis (serious, 1 patient) Muscular weakness (serious, 1 patient) Osteoarthritis (serious, 1 patient) Bradycardia (below serious, 1 patient) Cardiac failure congestive (below serious, 1 patient) Ventricular extrasystoles (below serious, 1 patient) Dry eye (below serious, 4 patients) Discharge eye (below serious, 1 patient) Eye haemorrhage (below serious, 1 patient) Eye oedema (below serious, 1 patient) Eye swelling (below serious, 1 patient) Vitreous floaters (below serious, 1 patient) Abdominal discomfort (below serious, 1 patient) Abdominal distension (below serious, 2 patients) Constipation (below serious, 31 patient) Diarrhoea (below serious, 8 patients) Dry mouth (below serious, 66 patients) Dyspepsia (below serious, 7 patients) Faecal incontinence (below serious, 1 patient) Flatulence (below serious, 2 patients) Gastrooesophageal reflux disease (below serious, 3 patients) Haemorrhoids (below serious, 1 patient) Hiatus hernia (below serious, 1 patient) Nausea (below serious, 5 patients) Tongue dry (below serious, 1 patient) Fatigue (below serious, 8 patients) Local swelling (below serious, 1 patient) Oedema (below serious, 1 patient) Therapeutic response unexpected (below serious, 1 patient) Candidiasis (below serious, 1 patient) Diverticulitis (below serious, 1 patient) Herpes simplex (below serious, 1 patient) Herpes zoster ophthalmic (below serious, 1 patient) Oral herpes (below serious, 1 patient) Pneumonia viral (below serious, 1 patient) Sinusitis (below serious, 5 patients) Tinea pedis (below serious, 1 patient) Tooth abscess (below serious, 1 patient) Vulvovaginal candidiasis (below serious, 1 patient) Arthropod bite (below serious, 1 patient) Contusion (below serious, 3 patients) Laceration (below serious, 1 patient) Post procedural haematoma (below serious, 1 patient) Skeletal injury (below serious, 2 patients) Blood glucose increased (below serious, 1 patient) Blood pressure increased (below serious, 2 patients) Blood uric acid increased (below serious, 1 patient) International normalised ratio increased (below serious, 1 patient) Residual urine volume increased (below serious, 1 patient) Weight increased (below serious, 1 patient) Gout (below serious, 2 patients) Type 2 diabetes mellitus (below serious, 1 patient) Back pain (below serious, 4 patients) Bursitis (below serious, 1 patient) Intervertebral disc degeneration (below serious, 1 patient) Musculoskeletal chest pain (below serious, 1 patient) Musculoskeletal pain (below serious, 2 patients) Osteoporosis (below serious, 1 patient) Trigger finger (below serious, 1 patient) Skin cancer (below serious, 1 patient) Diabetic neuropathy (below serious, 1 patient) Dizziness (below serious, 3 patients) Headache (below serious, 7 patients) Hypersomnia (below serious, 1 patient) Memory impairment (below serious, 2 patients) Migraine (below serious, 1 patient) Sinus headache (below serious, 1 patient) Tremor (below serious, 1 patient) Confusional state (below serious, 1 patient) Depression (below serious, 1 patient) Sleep disorder (below serious, 1 patient) Dysuria (below serious, 4 patients) Nephrolithiasis (below serious, 1 patient) Urinary hesitation (below serious, 1 patient) Urinary retention (below serious, 9 patients) Urine odour abnormal (below serious, 1 patient) Haemorrhage vaginal (below serious, 1 patient) Asthma (below serious, 1 patient) Bronchospasm (below serious, 1 patient) Chronic obstructive pulmonary disease (below serious, 2 patients) Cough (below serious, 7 patients) Dry throat (below serious, 5 patients) Dysphonia (below serious, 1 patient) Dyspnoea exertional (below serious, 1 patient) Epistaxis (below serious, 1 patient) Nasal dryness (below serious, 1 patient) Oropharyngeal pain (below serious, 2 patients) Allergic rhinitis (below serious, 1 patient) Sinus congestion (below serious, 2 patients) Blister (below serious, 1 patient) Ingrowing nail (below serious, 1 patient) Onychoclasis (below serious, 1 patient) Pruritus (below serious, 2 patients) Generalised pruritus (below serious, 1 patient) Urticaria (below serious, 1 patient) Flushing (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT00928070
28 mg 1 times / day multiple, oral Highest studied dose Dose: 28 mg, 1 times / day Route: oral Route: multiple Dose: 28 mg, 1 times / day Sources: https://ec.europa.eu/health/documents/community-register/2012/20121025124795/anx_124795_en.pdf Page: p.9, 18	unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: https://ec.europa.eu/health/documents/community-register/2012/20121025124795/anx_124795_en.pdf Page: p.9, 18	Sources: https://ec.europa.eu/health/documents/community-register/2012/20121025124795/anx_124795_en.pdf Page: p.9, 18
8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022030s007lbl.pdf Page: p.4	unhealthy n = 785 Health Status: unhealthy Condition: Overactive bladder Population Size: 785 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022030s007lbl.pdf Page: p.4	Disc. AE: Dry mouth... AEs leading to discontinuation/dose reduction: Dry mouth (0.8%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022030s007lbl.pdf Page: p.4
8 mg 1 times / day multiple, oral Recommended Dose: 8 mg, 1 times / day Route: oral Route: multiple Dose: 8 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022030s007lbl.pdf Page: p.1	unhealthy Health Status: unhealthy Condition: Overactive bladder Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022030s007lbl.pdf Page: p.1	Disc. AE: Face angioedema, Lip angioedema... AEs leading to discontinuation/dose reduction: Face angioedema Lip angioedema Oedema tongue Angioedema of larynx Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022030s007lbl.pdf Page: p.1
8 mg 1 times / day steady, oral Dose: 8 mg, 1 times / day Route: oral Route: steady Dose: 8 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00832650	healthy n = 25 Health Status: healthy Sex: F Population Size: 25 Sources: https://clinicaltrials.gov/ct2/show/NCT00832650	Other AEs: Dry eye, Abdominal pain... Other AEs: Dry eye (below serious, 1 patient) Abdominal pain (below serious, 2 patients) Constipation (below serious, 1 patient) Diarrhoea (below serious, 2 patients) Dry mouth (below serious, 13 patients) Dyschezia (below serious, 1 patient) Oedema peripheral (below serious, 1 patient) Nasopharyngitis (below serious, 2 patients) Headache (below serious, 12 patients) Pollakiuria (below serious, 1 patient) Dry throat (below serious, 1 patient) Oropharyngeal pain (below serious, 1 patient) Sources: https://clinicaltrials.gov/ct2/show/NCT00832650
8 mg 1 times / day steady, oral Dose: 8 mg, 1 times / day Route: oral Route: steady Dose: 8 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00862745	unhealthy n = 322 Health Status: unhealthy Condition: Urge Urinary Incontinence Sex: F Population Size: 322 Sources: https://clinicaltrials.gov/ct2/show/NCT00862745	Other AEs: Myocardial infarction, Embolus pulmonary... Other AEs: Myocardial infarction (serious, 1 patient) Embolus pulmonary (serious, 1 patient) Breast cancer (serious, 1 patient) Colitis (serious, 1 patient) Constipation (below serious, 24 patients) Headache (below serious, 19 patients) Cold (below serious, 21 patient) Urinary tract infection (below serious, 17 patients) Cough (below serious, 10 patients) Nausea (below serious, 10 patients) Dyspepsia (below serious, 9 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00862745
8 mg 1 times / day steady, oral (max) Dose: 8 mg, 1 times / day Route: oral Route: steady Dose: 8 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00546637	unhealthy n = 471 Health Status: unhealthy Condition: Overactive Bladder Sex: M Population Size: 471 Sources: https://clinicaltrials.gov/ct2/show/NCT00546637	Other AEs: Myocardial infarction, Colitis ulcerative... Other AEs: Myocardial infarction (serious, 1 patient) Colitis ulcerative (serious, 1 patient) Cellulitis staphylococcal (serious, 1 patient) Genitourinary tract infection (serious, 1 patient) Intervertebral disc protrusion (serious, 1 patient) Lung neoplasm malignant (serious, 1 patient) Transitional cell carcinoma (serious, 1 patient) Dysuria (serious, 1 patient) Colic renal (serious, 1 patient) Testicular torsion (serious, 1 patient) Orthostatic hypotension (serious, 1 patient) Abdominal pain (below serious, 6 patients) Constipation (below serious, 31 patient) Diarrhoea (below serious, 9 patients) Dry mouth (below serious, 100 patients) Dyspepsia (below serious, 9 patients) Gastritis (below serious, 5 patients) Nausea (below serious, 6 patients) Influenza (below serious, 6 patients) Nasopharyngitis (below serious, 5 patients) Sinusitis (below serious, 5 patients) Headache (below serious, 15 patients) Insomnia (below serious, 9 patients) Dysuria (below serious, 15 patients) Urinary retention (below serious, 11 patient) Erectile dysfunction (below serious, 5 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00546637
8 mg 1 times / day steady, oral Dose: 8 mg, 1 times / day Route: oral Route: steady Dose: 8 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00444925	unhealthy n = 679 Health Status: unhealthy Condition: Overactive Bladder Population Size: 679 Sources: https://clinicaltrials.gov/ct2/show/NCT00444925	Other AEs: Anaemia iron deficiency, Hypertensive heart disease... Other AEs: Anaemia iron deficiency (serious, 1 patient) Hypertensive heart disease (serious, 1 patient) Myocardial ischaemia (serious, 1 patient) Abdominal pain (serious, 1 patient) Appendicitis perforated (serious, 1 patient) Rectal haemorrhage (serious, 1 patient) Bronchiectasis (serious, 1 patient) Traumatic brain injury (serious, 1 patient) Upper limb fracture (serious, 1 patient) Intervertebral disc protrusion (serious, 1 patient) Hepatic neoplasm malignant (serious, 1 patient) Prostate cancer (serious, 1 patient) Haemorrhage intracranial (serious, 1 patient) Suicidal behaviour (serious, 1 patient) Urinary incontinence (serious, 1 patient) Haemorrhage uterine (serious, 1 patient) Vision blurred (below serious, 12 patients) Abdominal pain (below serious, 10 patients) Abdominal pain upper (below serious, 9 patients) Constipation (below serious, 37 patients) Diarrhoea (below serious, 14 patients) Dry mouth (below serious, 189 patients) Dyspepsia (below serious, 12 patients) Vomiting (below serious, 7 patients) Fatigue (below serious, 12 patients) Urinary tract infection (below serious, 15 patients) Dizziness (below serious, 8 patients) Headache (below serious, 38 patients) Dysuria (below serious, 4 patients) Cough (below serious, 8 patients) Hypertension (below serious, 8 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00444925
8 mg 1 times / day steady, oral (max) Dose: 8 mg, 1 times / day Route: oral Route: steady Dose: 8 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT00911937	unhealthy n = 463 Health Status: unhealthy Condition: Overactive Bladder Population Size: 463 Sources: https://clinicaltrials.gov/ct2/show/NCT00911937	Other AEs: Septic arthritis staphylococcal, Ankle fracture... Other AEs: Septic arthritis staphylococcal (serious, 1 patient) Ankle fracture (serious, 1 patient) Fall (serious, 1 patient) Hip fracture (serious, 1 patient) Tibia fracture (serious, 1 patient) Diabetic ketoacidosis (serious, 1 patient) Lymphoma (serious, 1 patient) Renal failure acute (serious, 1 patient) Otorrhoea (below serious, 1 patient) Hypothyroidism (below serious, 1 patient) Dry eye (below serious, 9 patients) Abdominal pain (below serious, 4 patients) Abdominal pain upper (below serious, 2 patients) Colitis (below serious, 1 patient) Constipation (below serious, 15 patients) Dry mouth (below serious, 98 patients) Dyspepsia (below serious, 5 patients) Dysphagia (below serious, 1 patient) Gastritis (below serious, 1 patient) Gastrooesophageal reflux disease (below serious, 2 patients) Haemorrhoids (below serious, 1 patient) Lip dry (below serious, 1 patient) Rectal prolapse (below serious, 1 patient) Stomatitis (below serious, 1 patient) Asthenia (below serious, 2 patients) Fatigue (below serious, 5 patients) Feeling abnormal (below serious, 1 patient) Gait disturbance (below serious, 1 patient) Oedema (below serious, 1 patient) Acute sinusitis (below serious, 1 patient) Bronchitis (below serious, 1 patient) Cystitis (below serious, 2 patients) Diverticulitis (below serious, 1 patient) Gastroenteritis (below serious, 2 patients) Gastroenteritis viral (below serious, 1 patient) Herpes zoster (below serious, 2 patients) Pharyngitis streptococcal (below serious, 1 patient) Pneumonia primary atypical (below serious, 1 patient) Tooth infection (below serious, 1 patient) Upper respiratory tract infection (below serious, 5 patients) Urinary tract infection (below serious, 9 patients) Foot fracture (below serious, 1 patient) Muscle injury (below serious, 1 patient) Muscle strain (below serious, 2 patients) Periorbital haematoma (below serious, 1 patient) Procedural pain (below serious, 1 patient) Blood glucose decreased (below serious, 1 patient) Blood pressure increased (below serious, 2 patients) Urine output decreased (below serious, 1 patient) Hyperlipidaemia (below serious, 1 patient) Hypertriglyceridaemia (below serious, 1 patient) Pica (below serious, 1 patient) Polydipsia (below serious, 1 patient) Type 2 diabetes mellitus (below serious, 2 patients) Arthralgia (below serious, 3 patients) Arthritis (below serious, 1 patient) Bursitis (below serious, 1 patient) Flank pain (below serious, 3 patients) Muscle spasms (below serious, 2 patients) Muscular weakness (below serious, 1 patient) Myalgia (below serious, 2 patients) Myositis (below serious, 1 patient) Neck pain (below serious, 1 patient) Pain in extremity (below serious, 2 patients) Basal cell carcinoma (below serious, 1 patient) Amnesia (below serious, 1 patient) Dizziness (below serious, 6 patients) Headache (below serious, 11 patient) Lethargy (below serious, 1 patient) Memory impairment (below serious, 1 patient) Nerve compression (below serious, 1 patient) Paraesthesia (below serious, 1 patient) Syncope (below serious, 1 patient) Tremor (below serious, 1 patient) Depression (below serious, 2 patients) Insomnia (below serious, 5 patients) Dysuria (below serious, 2 patients) Haematuria (below serious, 1 patient) Nephrolithiasis (below serious, 1 patient) Polyuria (below serious, 1 patient) Urinary hesitation (below serious, 2 patients) Urinary incontinence (below serious, 1 patient) Urinary retention (below serious, 3 patients) Urine flow decreased (below serious, 1 patient) Chronic obstructive pulmonary disease (below serious, 1 patient) Dry throat (below serious, 3 patients) Dysphonia (below serious, 2 patients) Dyspnoea (below serious, 1 patient) Epistaxis (below serious, 1 patient) Nasal congestion (below serious, 3 patients) Nasal dryness (below serious, 3 patients) Oropharyngeal pain (below serious, 3 patients) Rhinorrhoea (below serious, 2 patients) Throat irritation (below serious, 1 patient) Dermatitis contact (below serious, 1 patient) Eczema (below serious, 1 patient) Generalised pruritus (below serious, 1 patient) Flushing (below serious, 1 patient) Hypertension (below serious, 3 patients) Vision blurred (below serious, 4 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT00911937
8 mg 1 times / day steady, oral Dose: 8 mg, 1 times / day Route: oral Route: steady Dose: 8 mg, 1 times / day Sources: https://clinicaltrials.gov/ct2/show/NCT01302054	unhealthy n = 308 Health Status: unhealthy Condition: Overactive Bladder Population Size: 308 Sources: https://clinicaltrials.gov/ct2/show/NCT01302054	Other AEs: Angina pectoris, Myocardial infarction... Other AEs: Angina pectoris (serious, 1 patient) Myocardial infarction (serious, 1 patient) Prostate cancer (serious, 1 patient) Chronic obstructive pulmonary disease (serious, 1 patient) Hypertension (serious, 1 patient) Vision blurred (below serious, 3 patients) Constipation (below serious, 12 patients) Dry mouth (below serious, 51 patient) Dyspepsia (below serious, 6 patients) Sources: https://clinicaltrials.gov/ct2/show/NCT01302054

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1579 inducer 768 substrate 1709	inhibitor 1752 inducer 383	inhibitor 1837 substrate 1193	inhibitor 1599

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1509 CYP2B6 799 CYP2C8 901 CYP2C19 1463 CYP2E1 876 P-gp 1437	P-gp 1527	CYP1A2 689 CYP2B6 538 CYP2C19 290

Drug as perpetrator

Target	Modality	Activity	Metabolite
CYP1A2 1673	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP1A2 1673	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2B6 985	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2B6 985	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2C19 1537	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2C19 1537	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2C8 955	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2C9 1803	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2C9 1803	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2D6 1875	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP2E1 964	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP3A4 1909	inducer 1542 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
CYP3A4 1909	inhibitor 3240 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/022030s014lbl.pdf#page=12 Page: 12.0	no	SPM 7605 5
P-gp 1626	inhibitor 3240 Sources: https://www.ema.europa.eu/en/documents/scientific-discussion/toviaz-epar-scientific-discussion_en.pdf#page=18 Page: 18.0	weak
L-type Ca2+ 7	supressor 155 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022030s000_PharmR_P1.pdf#page=58 Page: 58.0	yes [Inhibition 15 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1527	substrate 3326 Sources: https://www.ema.europa.eu/en/documents/scientific-discussion/toviaz-epar-scientific-discussion_en.pdf#page=15 Page: 15.0	yes
CYP3A4 1709	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022030s000_ClinPharmR.pdf#page=38 Page: 38.0	yes	SPM 7605 5	yes (co-administration study) Comment: Following blockade of CYP3A4 by coadministration of the potent CYP3A4 inhibitor ketoconazoles, Cmax and AUC of the active metabolite of fesoterodine increased 2.0- and 2.3-fold, respectively, after oral administration of Toviaz to CYP2D6 extensive metabolizers. In CYP2D6 poor metabolizers, Cmax and AUC of the active metabolite of fesoterodine increased 2.1- and 2.5-fold, respectively, during coadministration of ketoconazole. Cmax and AUC were 4.5- and 5.7-fold higher, respectively, in subjects who were CYP2D6 poor metabolizers and taking ketoconazole; Following induction of CYP3A4 by coadministration of rifampicin (inducer), Cmax and AUC of the active metabolite of fesoterodine decreased by approximately 70% and 75%, respectively, after oral administration of Toviaz Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022030s000_ClinPharmR.pdf#page=38 Page: 38.0
CYP2D6 1193	substrate 3326 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022030s000_ClinPharmR.pdf#page=38 Page: 38.0	yes	SPM 7605 5	yes (pharmacogenomic study) Comment: CYP2D6 PMs have values for AUC and Cmax that are about 2-fold higher that CYP2D6 EMs Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022030s000_ClinPharmR.pdf#page=38 Page: 38.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1632	inhibitor 1613 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2008/022030s000_PharmR_P1.pdf#page=57 Page: 57.0

Sourcing

Vendor/Aggregator	ID	URL
AK Scientific, Inc. (AKSCI)	X5024	http://www.aksci.com/item_detail.php?cat=X5024
Aaron Chemicals	AR00BFSC	http://www.aaronchem.com/286930-02-7
Achemtek	0102-020049	http://www.achemtek.com/286930-02-7
BLD Pharm	BD262927	http://www.bldpharm.com/products/286930-02-7.html
Chem Scene	CS-M2392	http://www.chemscene.com/286930-02-7.html
ChemMol	44025744	http://www.chemmol.com/chemmol/44025744.html
ChemMol	49400560	http://www.chemmol.com/chemmol/49400560.html
ChemMol	49401416	http://www.chemmol.com/chemmol/49401416.html
ChemMol	99063804	http://www.chemmol.com/chemmol/99063804.html
Chemspace	CSSB00020617528	https://chem-space.com/CSSB00020617528
Clearsynth	CS-O-30922	http://www.clearsynth.com/en/CSO30922.html
DC Chemicals	DC23515	http://www.dcchemicals.com/product_show-DC23515.html
Hairui	HR106732	http://www.hairuichem.com/en/product/250214-44-9.html
MedChem Express	HY-70053	https://www.medchemexpress.com/fesoterodine.html
OChem	26230	http://www.ocheminc.com/index.php?act=psearch&pid=930F027
Smolecule	S623538	https://www.smolecule.com/products/s623538
THE BioTek	bt-337449	https://www.thebiotek.com/product/others/bt-337449
THE BioTek	bt-463777	https://www.thebiotek.com/product/others/bt-463777
eNovation Chemicals	D679729	https://www.enovationchem.com/ProductDetails.asp?ProductID=D679729
eNovation Chemicals	Y1048270	https://www.enovationchem.com/ProductDetails.asp?ProductID=Y1048270

PubMed

Title	Date	PubMed
Tolterodine--a new bladder selective muscarinic receptor antagonist: preclinical pharmacological and clinical data.	1997	9121357
Gateways to clinical trials.	2002 Dec	12616965
Gateways to clinical trials.	2003 Jun	12851663
Gateways to clinical trials.	2006 Dec	17235418
Gateways to clinical trials.	2006 Jul-Aug	16894408
Treatment of the overactive bladder syndrome with muscarinic receptor antagonists: a matter of metabolites?	2006 Nov	17021853
Efficacy, safety and tolerability of fesoterodine for overactive bladder syndrome.	2007 Dec	17937959
Clinical efficacy, safety, and tolerability of once-daily fesoterodine in subjects with overactive bladder.	2007 Oct	17651893
Overactive bladder: treatment options in primary care medicine.	2007 Sep	17908830
Pharmacological characterization of a novel investigational antimuscarinic drug, fesoterodine, in vitro and in vivo.	2008 Apr	18279452
Toviaz approved for overactive bladder.	2008 Dec 1	19020177
Fesoterodine for the treatment of urinary incontinence and overactive bladder.	2009	19956551
The safety and efficacy of tolterodine extended release in the treatment of overactive bladder in the elderly.	2009	19503781
Effects of flexible-dose fesoterodine on overactive bladder symptoms and treatment satisfaction: an open-label study.	2009 Apr	19348029
Practical aspects of lifestyle modifications and behavioural interventions in the treatment of overactive bladder and urgency urinary incontinence.	2009 Aug	19575724
A meta-analysis of the placebo response in antimuscarinic drug trials for overactive bladder.	2009 Jul 22	19624824
Influence of food on the pharmacokinetic profile of fesoterodine.	2009 Jun	19473600
Evaluation of drug-drug interactions with fesoterodine.	2009 Jun	19347334
New drugs: milnacipran hydrochloride, fesoterodine fumarate, and silodosin.	2009 Mar-Apr	19289354
Fesoterodine (toviaz) for overactive bladder.	2009 May 4	19417719
Tolterodine extended-release for overactive bladder.	2009 Sep	19663610
Durability of treatments for overactive bladder.	2010 Apr	20456203
Efficacy of fesoterodine over 24 hours in subjects with overactive bladder.	2010 Apr	20121659
The cost-effectiveness of solifenacin vs fesoterodine, oxybutynin immediate-release, propiverine, tolterodine extended-release and tolterodine immediate-release in the treatment of patients with overactive bladder in the UK National Health Service.	2010 Aug	20653664
Spinal effects of the fesoterodine metabolite 5-hydroxymethyl tolterodine and/or doxazosin in rats with or without partial urethral obstruction.	2010 Aug	20639056
The cost-effectiveness of solifenacin vs fesoterodine, oxybutynin immediate-release, propiverine, tolterodine extended-release and tolterodine immediate-release in the treatment of patients with overactive bladder in the UK National Health Service.	2010 Aug	20132203
Modeling dose-response relationships of the effects of fesoterodine in patients with overactive bladder.	2010 Aug 19	20723260
The pharmacokinetic profile of fesoterodine 8 mg with daytime or nighttime dosing.	2010 Feb	19915829
New Drugs2010, PART 1.	2010 Feb	20083979
Recent advances in management of bladder overactivity.	2010 Feb 11	20948824
Urodynamic evaluation of fesoterodine metabolite, doxazosin and their combination in a rat model of partial urethral obstruction.	2010 Jul	19888972

Patents

Sample Use Guides

In Vivo Use Guide

2-203 nM/kg [0.001-0.1 mg/kg]

Route of Administration: Intravenous

In Vitro Use Guide

In terms of IC50 values (mean of 3-6 experiments), Desfesoterodine was >900 times more potent in blocking bladder muscarinic receptors (IC50 5.7 nM) than calcium channels (papillary muscle: IC50 5.4 uM; atrium: IC50 15 uM, bladder IC50 39 uM), alph-adrenoceptors (portal vein: IC50 100 uM) and histamine receptors (ileum: IC50 6.1 uM).

Substance Class	Chemical Created by `admin` on `Thu Jul 06 00:06:51 UTC 2023` Edited by `admin` on `Thu Jul 06 00:06:51 UTC 2023`
Record UNII	YU871O78GR
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DESFESOTERODINE

Official Name

English

(+)-N,N-DIISOPROPYL-3-(2-HYDROXY-5-HYDROXYMETHYLPHENYL)-3-PHENYLPROPYLAMINE

Systematic Name

English

SPM-7605

Code

English

(R)-(+)-2-(3-DIISOPROPYLAMINO-1-PHENYLPROPYL)-4-HYDROXYMETHYLPHENOL

Systematic Name

English

desfesoterodine [INN]

Common Name

English

Desfesoterodine [WHO-DD]

Common Name

English

5-HYDROXYMETHYLTOLTERODINE

Common Name

English

PNU-200577

Code

English

BENZENEMETHANOL, 3-((1R)-3-(BIS(1-METHYLETHYL)AMINO)-1-PHENYLPROPYL)-4-HYDROXY-

Systematic Name

English

Classification Tree Code System Code

WHO-ATC

G04BD13