brotizolam 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
diazepam derivatives	409	57801-81-7

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: brotizolam mederantil lendorm	Molecular weight: 393.69 Formula: C15H10BrClN4S CLOGP: 2.86 LIPINSKI: 0 HAC: 4 HDO: 0 TPSA: 43.07 ALOGS: -3.83 ROTB: 1

Molecule

Description

Molfile Inchi Smiles

Synonyms:

brotizolam
mederantil
lendorm

Molecular weight: 393.69
Formula: C15H10BrClN4S
CLOGP: 2.86
LIPINSKI: 0
HAC: 4
HDO: 0
TPSA: 43.07
ALOGS: -3.83
ROTB: 1

Drug dosage:

Dose	Unit	Route
0.25	mg	O

ADMET properties:

Property	Value	Reference
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.01 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Hosey CM, Chan R, Benet LZ
BA (Bioavailability)	70 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	0.75 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	2 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.09 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	4.80 hours	Lombardo F, Berellini G, Obach RS
S (Water solubility)	0.01 mg/mL	Bocci G, Oprea TI, Benet LZ

Approvals:

Date	Agency	Company	Orphan
Jan. 1, 1983	YEAR INTRODUCED

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Hepatic function abnormal	109.10	18.48	60	6494	37082	63445386
Altered state of consciousness	97.56	18.48	49	6505	25181	63457287
Platelet count decreased	84.20	18.48	80	6474	116042	63366426
Interstitial lung disease	69.96	18.48	55	6499	61853	63420615
Decreased appetite	66.90	18.48	104	6450	250948	63231520
Neutrophil count decreased	65.65	18.48	51	6503	56355	63426113
Anaemia	65.26	18.48	112	6442	293318	63189150
Distributive shock	64.42	18.48	17	6537	1366	63481102
Suicide attempt	62.19	18.48	51	6503	60867	63421601
Sopor	60.12	18.48	34	6520	22130	63460338
Cardiac failure	58.16	18.48	58	6496	89084	63393384
Fatigue	57.85	18.48	11	6543	888017	62594451
Malignant catatonia	51.86	18.48	10	6544	190	63482278
Drug ineffective	46.84	18.48	25	6529	1044740	62437728
Drug abuse	43.31	18.48	45	6509	72473	63409995
Drug eruption	42.48	18.48	30	6524	28664	63453804
Gamma-glutamyltransferase increased	37.91	18.48	30	6524	34001	63448467
Cerebral infarction	37.75	18.48	26	6528	23867	63458601
Iron deficiency anaemia	37.01	18.48	24	6530	19945	63462523
Neuroleptic malignant syndrome	34.06	18.48	19	6535	12037	63470431
White blood cell count decreased	32.01	18.48	54	6500	139050	63343418
Erythema multiforme	31.41	18.48	17	6537	10152	63472316
Overdose	29.61	18.48	47	6507	115031	63367437
Osteonecrosis of jaw	28.89	18.48	26	6528	35097	63447371
Malignant neoplasm progression	27.55	18.48	38	6516	82083	63400385
Intentional overdose	27.45	18.48	36	6518	74116	63408352
Pain	27.28	18.48	22	6532	740606	62741862
Lymphocyte count decreased	26.07	18.48	23	6531	30234	63452234
Alopecia	24.57	18.48	3	6551	337533	63144935
Pyrexia	23.99	18.48	104	6450	470374	63012094
Renal impairment	23.99	18.48	37	6517	88318	63394150
Febrile neutropenia	23.37	18.48	43	6511	118406	63364062
Vasoplegia syndrome	22.74	18.48	8	6546	1691	63480777
Lip erosion	22.67	18.48	7	6547	986	63481482
Hyponatraemia	22.56	18.48	41	6513	111859	63370609
Bradyphrenia	22.48	18.48	12	6542	6968	63475500
Oromandibular dystonia	22.28	18.48	6	6548	521	63481947
Hypokalaemia	22.16	18.48	39	6515	103765	63378703
Drug withdrawal syndrome neonatal	21.16	18.48	8	6546	2073	63480395
Hepatocellular carcinoma	20.75	18.48	8	6546	2186	63480282
Hypersensitivity	20.34	18.48	3	6551	292682	63189786
Psychiatric symptom	19.75	18.48	10	6544	5213	63477255
Intracranial pressure increased	19.74	18.48	10	6544	5217	63477251
Concomitant disease aggravated	19.50	18.48	12	6542	9100	63473368
Dyskinesia	19.34	18.48	20	6534	31982	63450486
Rhabdomyolysis	18.90	18.48	23	6531	43928	63438540
Swelling	18.73	18.48	3	6551	275375	63207093

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Hepatic function abnormal	105.04	18.46	78	6499	44285	34906069
Altered state of consciousness	87.05	18.46	54	6523	22839	34927515
Interstitial lung disease	84.43	18.46	81	6496	65201	34885153
Platelet count decreased	46.75	18.46	82	6495	119635	34830719
Pneumonia aspiration	44.91	18.46	47	6530	41856	34908498
Suicide attempt	42.14	18.46	44	6533	39072	34911282
Decreased appetite	37.68	18.46	91	6486	166301	34784053
Fatigue	35.15	18.46	13	6564	370640	34579714
Neutrophil count decreased	34.16	18.46	45	6532	51059	34899295
Renal impairment	32.12	18.46	61	6516	94452	34855902
Drug ineffective	31.62	18.46	24	6553	456727	34493627
Drug eruption	30.13	18.46	27	6550	19871	34930483
Disseminated intravascular coagulation	29.91	18.46	28	6549	21788	34928566
Blood creatine phosphokinase increased	29.21	18.46	39	6538	44818	34905536
Hyperuricaemia	28.10	18.46	18	6559	8025	34942329
Liver disorder	25.11	18.46	31	6546	32966	34917388
Pyrexia	24.99	18.46	126	6451	332887	34617467
Hypoglycaemia	23.34	18.46	39	6538	54601	34895753
Enterocolitis	23.29	18.46	16	6561	8010	34942344
Pneumonia	22.99	18.46	131	6446	362496	34587858
Cardiac failure	22.89	18.46	52	6525	91196	34859158
Cerebral infarction	22.86	18.46	27	6550	27428	34922926
White blood cell count increased	19.79	18.46	31	6546	41120	34909234
Asthenia	19.47	18.46	11	6566	245240	34705114
Malignant neoplasm progression	18.65	18.46	47	6530	87999	34862355

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Hepatic function abnormal	200.75	16.17	135	13340	72972	79657941
Altered state of consciousness	175.90	16.17	103	13372	43719	79687194
Interstitial lung disease	137.38	16.17	129	13346	112471	79618442
Platelet count decreased	128.19	16.17	161	13314	194503	79536410
Suicide attempt	97.26	16.17	93	13382	82839	79648074
Decreased appetite	95.62	16.17	191	13284	342227	79388686
Neutrophil count decreased	94.68	16.17	97	13378	93862	79637051
Fatigue	90.58	16.17	23	13452	929704	78801209
Drug ineffective	72.54	16.17	47	13428	1080866	78650047
Anaemia	70.44	16.17	199	13276	444816	79286097
Cardiac failure	68.70	16.17	106	13369	154736	79576177
Drug eruption	64.67	16.17	56	13419	43879	79687034
Pneumonia aspiration	61.81	16.17	66	13409	66901	79664012
Cerebral infarction	58.85	16.17	54	13421	45622	79685291
Sopor	58.81	16.17	47	13428	32963	79697950
White blood cell count decreased	51.19	16.17	104	13371	188184	79542729
Malignant neoplasm progression	48.00	16.17	84	13391	135906	79595007
Renal impairment	47.53	16.17	91	13384	157692	79573221
Gamma-glutamyltransferase increased	45.43	16.17	51	13424	54629	79676284
Neuroleptic malignant syndrome	44.38	16.17	37	13438	27522	79703391
Disseminated intravascular coagulation	43.51	16.17	41	13434	35801	79695112
Pyrexia	41.77	16.17	225	13250	678484	79052429
Distributive shock	41.46	16.17	16	13459	2671	79728242
Pain	38.98	16.17	37	13438	703765	79027148
Lymphocyte count decreased	37.40	16.17	43	13432	47246	79683667
Liver disorder	36.99	16.17	53	13422	72364	79658549
Intentional overdose	35.51	16.17	64	13411	105896	79625017
Concomitant disease aggravated	35.32	16.17	24	13451	13143	79717770
Blood creatine phosphokinase increased	34.68	16.17	49	13426	66041	79664872
Malignant catatonia	33.75	16.17	9	13466	456	79730457
Erythema multiforme	33.30	16.17	26	13449	17625	79713288
Hyperuricaemia	32.83	16.17	22	13453	11777	79719136
Bradyphrenia	32.43	16.17	21	13454	10619	79720294
Upper respiratory tract inflammation	32.06	16.17	15	13460	4020	79726893
Rhabdomyolysis	31.67	16.17	60	13415	103071	79627842
Blood pressure decreased	30.71	16.17	58	13417	99408	79631505
Decubitus ulcer	29.36	16.17	23	13452	15664	79715249
Iron deficiency anaemia	28.57	16.17	28	13447	25644	79705269
Drug hypersensitivity	27.84	16.17	8	13467	298908	79432005
Overdose	27.69	16.17	81	13394	184125	79546788
Osteonecrosis of jaw	27.17	16.17	35	13440	43191	79687722
Asthenia	27.02	16.17	28	13447	511661	79219252
Blood lactate dehydrogenase increased	26.66	16.17	33	13442	39137	79691776
Product dose omission issue	26.26	16.17	5	13470	247532	79483381
Arthralgia	26.22	16.17	35	13440	571768	79159145
White blood cell count increased	26.18	16.17	46	13429	74587	79656326
Subdural haematoma	25.56	16.17	29	13446	31405	79699508
Water intoxication	25.04	16.17	8	13467	766	79730147
Hypersensitivity	24.45	16.17	7	13468	262232	79468681
Enterocolitis	24.44	16.17	20	13455	14492	79716421
Hypokalaemia	24.24	16.17	66	13409	143974	79586939
Restlessness	23.69	16.17	34	13441	46458	79684455
Pneumonia	23.50	16.17	191	13284	660055	79070858
Febrile neutropenia	23.48	16.17	89	13386	230910	79500003
Hypoglycaemia	22.84	16.17	52	13423	101542	79629371
Confusional state	22.35	16.17	13	13462	317984	79412929
Alopecia	21.89	16.17	6	13469	231349	79499564
Swelling	21.70	16.17	5	13470	216706	79514207
Loss of consciousness	21.64	16.17	70	13405	167873	79563040
Fibrin degradation products increased	21.12	16.17	6	13469	385	79730528
Hyponatraemia	21.03	16.17	72	13403	177776	79553137
Salivary hypersecretion	20.65	16.17	18	13457	14206	79716707
Radiation pneumonitis	20.54	16.17	11	13464	3922	79726991
Rheumatoid arthritis	20.50	16.17	5	13470	208465	79522448
Peripheral swelling	20.44	16.17	10	13465	269607	79461306
Embolic stroke	20.36	16.17	14	13461	7812	79723101
Paraesthesia	19.93	16.17	3	13472	176320	79554593
Hypokinesia	19.75	16.17	20	13455	19040	79711873
Pneumonia bacterial	19.52	16.17	20	13455	19311	79711602
Psychiatric symptom	19.29	16.17	13	13462	7022	79723891
Skin erosion	19.28	16.17	11	13464	4434	79726479
Dyskinesia	18.91	16.17	30	13445	44743	79686170
Oromandibular dystonia	18.85	16.17	7	13468	1051	79729862
Constipation	18.80	16.17	96	13379	282954	79447959
Pleural effusion	18.22	16.17	60	13415	145202	79585711
Cholangitis	18.21	16.17	16	13459	12760	79718153
Dyspnoea	18.10	16.17	79	13396	856946	78873967
Aspartate aminotransferase increased	18.05	16.17	58	13417	138583	79592330
Hypoalbuminaemia	17.91	16.17	20	13455	21277	79709636
Delirium	17.58	16.17	42	13433	84585	79646328
Femoral neck fracture	17.32	16.17	14	13461	9970	79720943
Drug-induced liver injury	17.32	16.17	36	13439	66081	79664832
Aortic dissection	17.22	16.17	10	13465	4165	79726748
Pharyngitis	17.11	16.17	20	13455	22355	79708558
Infusion related reaction	16.76	16.17	9	13466	230228	79500685
Lip erosion	16.22	16.17	7	13468	1553	79729360

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	N05CD09	NERVOUS SYSTEM PSYCHOLEPTICS HYPNOTICS AND SEDATIVES Benzodiazepine derivatives
MeSH PA	D002491	Central Nervous System Agents
MeSH PA	D002492	Central Nervous System Depressants
MeSH PA	D006993	Hypnotics and Sedatives

Drug Use | Suggest Off label Use Form| |View source of the data|

None

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	6.34	Basic
pKa2	4.87	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Platelet-activating factor receptor	GPCR	P25105	PTAFR_HUMAN		IC50	6.52		CHEMBL

External reference:

ID	Source
D01744	KEGG_DRUG
19790	RXNORM
C0054151	UMLSCUI
CHEBI:31308	CHEBI
CHEMBL32479	ChEMBL_ID
DB09017	DRUGBANK_ID
C020960	MESH_SUPPLEMENTAL_RECORD_UI
2451	PUBCHEM_CID
4549	INN_ID
5XZM1R3DKF	UNII
698050003	SNOMEDCT_US
004151	NDDF

Pharmaceutical products:

None