AMBROXOL

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C13H18Br2N2O
Molecular Weight	378.103
Optical Activity	NONE
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

NC1=C(CN[C@H]2CC[C@H](O)CC2)C=C(Br)C=C1Br

InChI

InChIKey=JBDGDEWWOUBZPM-XYPYZODXSA-N

InChI=1S/C13H18Br2N2O/c14-9-5-8(13(16)12(15)6-9)7-17-10-1-3-11(18)4-2-10/h5-6,10-11,17-18H,1-4,7,16H2/t10-,11-

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18680446
Curator's Comment: Description was created based on several sources, including http://adisinsight.springer.com/drugs/800035262 | https://www.ncbi.nlm.nih.gov/pubmed/23158495 | https://www.ncbi.nlm.nih.gov/pubmed/18482096 | https://www.ncbi.nlm.nih.gov/pubmed/19578116 | http://zywiebio.com/drug-development/therapeutic-areas-of-interest/gaucher-disease/

Ambroxol, a substituted benzylamine, is an active metabolite of bromhexine, which is itself a synthetic derivative of vasicine, the active principle extracted from the plant species Adhatoda vasica. Ambroxol is an expectorant exerting mucokinetic properties, mucociliary activity, stimulation of surfactant production, anti-inflammatory and antioxidative actions and the local anaesthetic effect. Ambroxol was discovered at and has been manufactured by Dr. Karl Thomae GmbH, a division of Boehringer Ingelheim. The ambroxol patent is expired and the drug is available as a generic product from many different companies. Ambroxol was originally developed by Boehringer Ingelheim as a OTC therapy for respiratory disorders related to excessive mucus. Ambroxol's indication is secretolytic therapy in acute and chronic bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport. Boehringer Ingelheim markets the product under various brand names such as Mucosolvan® and Lasolvan®. Ambroxol was identified and found to be a pH-dependent, mixed-type inhibitor of glucocerebrosidase (GCase). Its inhibitory activity was maximal at neutral pH, found in the endoplasmic reticulum, and undetectable at the acidic pH of lysosomes. The pH dependence of Ambroxol to bind and stabilize the enzyme was confirmed. Ambroxol increases both the lysosomal fraction and the enzymatic activity of several mutant GCase variants. This profile of Ambroxol would allow to bind and stabilize GCase in the endoplasmic reticulum (thus preventing its degradation within endoplasmic reticulum), but without affecting GCase in the lysosomes (thus allowing it to degrade glucosylceramide). Indeed, studies showed that Ambroxol treatment significantly increased N370S and F213I mutant GCase activity and protein levels in fibroblasts originally obtained from Gaucher patients. Gaucher's disease is caused by the deficiency of glucocerebrosidase; ambroxol is a chaperone that acts by binding to and stabilising glucocerebrosidase. Zywie (formerly ExSAR Corporation) and Belrose Pharma are developing ambroxol hydrochloride (BEL 0218) for the treatment of type III Gaucher's disease. .

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Beta-glucocerebrosidase 5 Target ID: CHEMBL2179 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23158495 \| https://www.ncbi.nlm.nih.gov/pubmed/19578116	Chaperone 14
surfactant homeostasis 7 Target ID: GO:0043129 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26560688 \| https://www.ncbi.nlm.nih.gov/pubmed/15694461	Modulator 846

Conditions

Condition	Modality	Highest Phase	Product
Gaucher's disease type I 5 Sources: http://adisinsight.springer.com/drugs/800035262 http://zywiebio.com/drug-development/therapeutic-areas-of-interest/gaucher-disease/	Primary	Phase II 1147	Unknown Approved Use Unknown
Gaucher's disease type III 7 Sources: http://adisinsight.springer.com/drugs/800035262 http://zywiebio.com/drug-development/therapeutic-areas-of-interest/gaucher-disease/	Primary	Phase I 438	Unknown Approved Use Unknown
Chronic obstructive pulmonary disease 175 Sources: http://meppo.com/pdf/drugs/1159-MUCOSOLVAN-1329487332.pdf	Primary	Approved 8583	MUCOSOLVAN Approved Use MUCOSOLVAN (ambroxol hydrochloride) is indicated for secretolytic therapy in acute and chronic bronchopulmonary diseases associated with abnormal mucus secretion and impaired mucus transport.

C_max

Value	Dose	Analyte	Population
30.5 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=62	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
30.7 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=62	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
29.9 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=63	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
30 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=63	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
28.3 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=65	0.3 mL/kg single, oral dose: 0.3 mL/kg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
60.3 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=66	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
28.985 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=69	45 mg single, oral dose: 45 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
35.256 ng/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=69	45 mg single, oral dose: 45 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
76.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32372294/	75 mg 1 times / day steady-state, oral dose: 75 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
96.4 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32372294/	30 mg 2 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

AUC

Value	Dose	Analyte	Population
200 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=62	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
198.8 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=62	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
216.6 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=63	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
213.1 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=63	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
226.4 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=65	0.3 mL/kg single, oral dose: 0.3 mL/kg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
482.1 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=66	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
579.462 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=69	45 mg single, oral dose: 45 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
689.543 ng × h/mL OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=69	45 mg single, oral dose: 45 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
1228 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32372294/	75 mg 1 times / day steady-state, oral dose: 75 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED
1147 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32372294/	30 mg 2 times / day steady-state, oral dose: 30 mg route of administration: Oral experiment type: STEADY-STATE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED

T_1/2

Value	Dose	Analyte	Population
8.8 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=63	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
8.9 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=63	15 mg single, oral dose: 15 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
3.2 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=65	0.3 mL/kg single, oral dose: 0.3 mL/kg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
8.7 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=66	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: CHILD sex: UNKNOWN food status: UNKNOWN
12.149 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=69	45 mg single, oral dose: 45 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
12.178 h OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=69	45 mg single, oral dose: 45 mg route of administration: Oral experiment type: SINGLE co-administered:	AMBROXOL plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
21.7% OTHER GOV'T https://www.info.pmda.go.jp/go/interview/1/470310_2239001F1696_1_004_1F.pdf#page=70			AMBROXOL serum	Homo sapiens
10% REVIEW https://pubmed.ncbi.nlm.nih.gov/30372367/			AMBROXOL plasma	Homo sapiens

Doses

Dose	Population	Adverse events
0.75 % 2 times / day multiple, intranasal Recommended Dose: 0.75 %, 2 times / day Route: intranasal Route: multiple Dose: 0.75 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2523279/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2523279/	Disc. AE: Contact allergy... AEs leading to discontinuation/dose reduction: Contact allergy Sources: https://pubmed.ncbi.nlm.nih.gov/2523279/
90 mg 3 times / day multiple, oral Recommended Dose: 90 mg, 3 times / day Route: oral Route: multiple Dose: 90 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24824664/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/24824664/	Disc. AE: Epileptic seizure... AEs leading to discontinuation/dose reduction: Epileptic seizure Sources: https://pubmed.ncbi.nlm.nih.gov/24824664/
40 mg/kg 4 times / day multiple, oral Highest studied dose Dose: 40 mg/kg, 4 times / day Route: oral Route: multiple Dose: 40 mg/kg, 4 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/26130623/	unhealthy, NEWBORN Health Status: unhealthy Age Group: NEWBORN Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/26130623/	Sources: https://pubmed.ncbi.nlm.nih.gov/26130623/

AEs

AE	Significance	Dose	Population
Contact allergy	Disc. AE	0.75 % 2 times / day multiple, intranasal Recommended Dose: 0.75 %, 2 times / day Route: intranasal Route: multiple Dose: 0.75 %, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2523279/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/2523279/
Epileptic seizure	Disc. AE	90 mg 3 times / day multiple, oral Recommended Dose: 90 mg, 3 times / day Route: oral Route: multiple Dose: 90 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/24824664/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/24824664/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252 substrate 1946	inhibitor 2438 substrate 1193	inhibitor 2507 substrate 1388	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2E1 1060 CYP2A6 879 OATP1B3 961 OATP1B1 1079 CYP2C19 2057 CYP1A2 2153	CYP2B6 776 P-gp 2052 CYP2E1 729 CYP2C19 1119 CYP1A2 1197 CYP2C8 810 CYP4A11 137 CYP2A6 626 CYP1A1 389

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE1MzQ3OSJ9fQ==	no [IC50 >10 uM]
CYP2A6 911	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE1MzQ3OSJ9fQ==	no [IC50 >10 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE1MzQ3OSJ9fQ==	no [IC50 >10 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE1MzQ3OSJ9fQ==	no [IC50 >10 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkw1MjgxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE1MzQ3OSJ9fQ==	no [IC50 >10 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTUzNDc5In19	no [IC50 >10 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTUzNDc5In19	yes [IC50 0.5574 uM]
OATP1B1 1095	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNjk3NjY4IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE1MTQ2MzQifX0=	yes [Inhibition 10 uM]
OATP1B3 970	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwxNzQzMTIxIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDE1MTQ2MzQifX0=	yes [Inhibition 10 uM]

Drug as victim

Target	Modality	Activity
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10659952/	major [Km 248 uM]
CYP1A1 389	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10659952/	no
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10659952/	no
CYP2A6 626	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10659952/	no
CYP2B6 776	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10659952/	no
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10659952/	no
CYP2C8 810	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10659952/	no
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10659952/	no
CYP2D6 1388	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10659952/	no
CYP2E1 729	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10659952/	no
CYP4A11 137	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/10659952/	no
P-gp 2052	substrate 4014 Sources: https://pubchem.ncbi.nlm.nih.gov/compound/2132#section=BioAssay-Results Page: 273 \| 277	no

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMTUzNDc5In19

PubMed

Title	Date	PubMed
[Model experiments of physiologic and pharmacologic interactions with epithelial ionic currents induced by stimulation of sensory receptors ].	2001	12514900
[Antioxidative features of ambroxol--usefulness in COPD].	2001	11928667
Pharmacoeconomic analysis of prescriptions in Italian pediatric general practice.	2002	15609152
Efficacy and tolerability of ambroxol hydrochloride lozenges in sore throat. Randomised, double-blind, placebo-controlled trials regarding the local anaesthetic properties.	2002	12040968
[Atelectasis following cesarean section. Personal experience].	2002 Apr	12032457
Pulmonary alveolar proteinosis successfully treated with ambroxol.	2002 Dec	12521210
Development of treatment for pulmonary alveolar proteinosis.	2002 Dec	12521191
[Mucolytics in acute and chronic respiratory tract disorders. II. Uses for treatment and antioxidant properties].	2002 Mar	12053601
Ambroxol suppresses influenza-virus proliferation in the mouse airway by increasing antiviral factor levels.	2002 May	12030738
Quantitative determination of ambroxol in tablets by derivative UV spectrophotometric method and HPLC.	2003 Apr 1	12684099
Determination of ambroxol in human plasma using LC-MS/MS.	2003 Jun 1	12763530
In vitro inhibition of human neutrophil histotoxicity by ambroxol: evidence for a multistep mechanism.	2003 Oct	14534155
Effect of twelve-months therapy with oral ambroxol in preventing exacerbations in patients with COPD. Double-blind, randomized, multicenter, placebo-controlled study (the AMETHIST Trial).	2004	14643168
Bioequivalence assessment of ambroxol tablet after a single oral dose administration to healthy male volunteers.	2004 Jan	14597158
[Clinical observation on Biyan Qingdu Granule and ambroxol hydrochloride in treating secretory otitis media].	2004 Jul	15339416
[Comparison of the effect of ambroxol and dexamethasone on the expression of pulmonary surfactant proteins in the fetal rat lungs].	2004 Jun	15265434
[Management of extensive burn accompanying severe inhalation injury].	2004 May	15151846
Simultaneous determination of roxithromycin and ambroxol hydrochloride in a new tablet formulation by liquid chromatography.	2004 Sep 3	15336374
Ambroxol, a Nav1.8-preferring Na(+) channel blocker, effectively suppresses pain symptoms in animal models of chronic, neuropathic and inflammatory pain.	2005 Dec	16182323
Effect of ambroxol, spirulina and vitamin-E in naphthalene induced cataract in female rats.	2005 Jan	15881859
[Prophylactic effect of ambroxol on acute hydrochloric acid aspiration - induced lung injury].	2005 Jun	15970105
Adsorptive stripping voltammetric determination of ambroxol.	2005 Mar	15801671
[Treatment of sore throat pain with ambroxol-containing lozenges. Results of a pharmacy supported patient questionnaire].	2005 Nov	16309023
Determination of roxithromycin in rat lung tissue by liquid chromatography-mass spectrometry.	2005 Sep 15	15899569
Effects of cigarette smoke on degranulation and NO production by mast cells and epithelial cells.	2005 Sep 19	16168067
The influence of ambroxol and capsaicin on the isolated rabbit bladder wall.	2005 Sep-Oct	16459489
[Ambroxol].	2006	17089236
Systematic review of clinical data with BNO-101 (Sinupret) in the treatment of sinusitis.	2006 Apr	16645287
The influence of variation of gastric pH on the gelation and release characteristics of in situ gelling pectin formulations.	2006 Apr 7	16473484
[Efficacy of intravenous or atomizing ambroxol for prevention of respiratory distress syndrome in preterm infants].	2006 Aug	16923362
Herbal medicines for the treatment of COPD: a systematic review.	2006 Aug	16880367
[Ambroxol-induced toxicoderma].	2006 Feb	16508607
D-MEKK1, the Drosophila orthologue of mammalian MEKK4/MTK1, and Hemipterous/D-MKK7 mediate the activation of D-JNK by cadmium and arsenite in Schneider cells.	2006 Feb 1	16451733
[Influence of ambroxol on paraquat-induced lung tissue injury and change of pulmonary surfactant-associated protein A in the experimental rats].	2006 Jun	16824340
Ambroxol for the prevention of acute upper respiratory disease.	2006 Jun	16820995
[Atomization inhalation of ambroxol as an auxiliary therapy for severe pneumonia in neonates].	2006 Jun	16787604
Comparison of the effects of four Na+ channel analgesics on TTX-resistant Na+ currents in rat sensory neurons and recombinant Nav1.2 channels.	2006 Mar 13	16293367
Ambroxol-induced modification of ion transport in human airway Calu-3 epithelia.	2006 May 5	16546120
Nutritional supplements and infection in the elderly: why do the findings conflict?	2006 Nov 23	17123445
[Ambroxol-induced immune hemolytic anemia].	2006 Oct	16790300
Safety and usage pattern of an over-the-counter ambroxol cough syrup: a community pharmacy-based cohort study.	2006 Sep	16995329
Proteases essential for human influenza virus entry into cells and their inhibitors as potential therapeutic agents.	2007	17311557
In situ gelling pectin formulations for oral drug delivery at high gastric pH.	2007 Apr 20	17141988
Post-marketing assessment of content and efficacy of preservatives in artemisinin-derived antimalarial dry suspensions for paediatric use.	2007 Jan 26	17257400
Simultaneous determination and pharmacokinetic study of roxithromycin and ambroxol hydrochloride in human plasma by LC-MS/MS.	2007 Jul	17462615
Determination of ambroxol in human plasma by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI).	2007 Jun 15	17446147
[Determination of ambroxol and clenbuterol in human plasma by LC-MS/MS method].	2007 Mar	17520832
Parenteral ambroxol treatment causes xanthine and calcium oxalate stones in rats.	2007 May	17511738
Solid-state chemistry of ambroxol theophylline-7-acetate.	2007 May	17455344
Action of neltenexine on anion secretion in human airway epithelia.	2007 May 18	17400191

Patents

Sample Use Guides

In Vivo Use Guide

Adults: daily dose of 30 mg (one Ambroxol tablet ) to 120 mg (4 Ambroxol tablets) taken in 2 to 3 divided doses Children up to 2 years: half a teaspoonful Ambroxol syrup twice daily Children 2 - 5 years: half a teaspoonful Ambroxol syrup 3 times daily Children over 5 years: One teaspoonful Ambroxol syrup 2-3 times daily.

Route of Administration: Oral

In Vitro Use Guide

Ambroxol exerted a biphasic response in surfactant secretion, with a significant increase at low concentrations (1 - 10 uM) and an inhibition at high concentrations (≥ 0.1 mM), which is beyond reported plasma Ambroxol concentrations in blood

Name

Type

Language

TABCIN

Preferred Name

English

AMBROXOL

Official Name

English

ambroxol [INN]

Common Name

English

Ambroxol [WHO-DD]

Common Name

English

AMBROXOL [MI]

Common Name

English

TRANS-4-((2-AMINO-3,5-DIBROMOBENZYL)AMINO)CYCLOHEXANOL

Systematic Name

English

4-HYDROXYDEMETHYLBROMHEXINE, TRANS-

Common Name

English

Classification Tree Code System Code

WHO-ATC

R03CC63