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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H24N2O8.3H2O
Molecular Weight 498.4804
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TETRACYCLINE TRIHYDRATE

SMILES

O.O.O.[H][C@@]12C[C@@]3([H])C(C(=O)C4=C(O)C=CC=C4[C@@]3(C)O)=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@H]2N(C)C

InChI

InChIKey=OVMPBWOOPZNLRQ-ZZEGOUJXSA-N
InChI=1S/C22H24N2O8.3H2O/c1-21(31)8-5-4-6-11(25)12(8)16(26)13-9(21)7-10-15(24(2)3)17(27)14(20(23)30)19(29)22(10,32)18(13)28;;;/h4-6,9-10,15,25,27-28,31-32H,7H2,1-3H3,(H2,23,30);3*1H2/t9-,10-,15-,21+,22-;;;/m0.../s1

HIDE SMILES / InChI

Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C22H24N2O8
Molecular Weight 444.4346
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Discovered as natural products from actinomycetes soil bacteria, the tetracyclines were first reported in the scientific literature in 1948. They were noted for their broad spectrum antibacterial activity and were commercialized with clinical success beginning in the late 1940s to the early 1950s. By catalytic hydrogenation of Aureomycin, using palladium metal and hydrogen, the C7 deschloro derivative was synthesized, producing a compound of higher potency, a better solubility profile, and favorable pharmacological activity; it was subsequently named tetracycline. Tetracyclines are primarily bacteriostatic and exert their antimicrobial effect by the inhibition of protein synthesis by binding to the 30S ribosomal subunit. Tetracycline is active against a broad range of gram-negative and gram-positive organisms. Tetracycline is indicated in the treatment of infections caused by susceptible strains. To reduce the development of drug-resistant bacteria and maintain the effectiveness of tetracycline hydrochloride and other antibacterial drugs, tetracycline hydrochloride should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Originator

Curator's Comment: References retrieved from https://www.ncbi.nlm.nih.gov/pubmed/13117662 # Pfizer and Lederle Laboratories

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
TETRACYCLINE HYDROCHLORIDE

Approved Use

Tetracycline is indicated in the treatment of infections caused by susceptible strains of the designated organisms in the conditions listed below: • Upper respiratory tract infections caused by Streptococcus pyogenes, Streptococcus pneumoniae and Hemophilus influenzae. Note: Tetracycline should not be used for streptococcal disease unless the organism has been demonstrated to be susceptible. • Lower respiratory tract infections caused by Streptococcus pyogenes, Streptococcus pneumoniae, Mycoplasma pneumoniae (Eaton agent, and Klebsiella sp.) • Skin and soft tissue infections caused by Streptococcus pyogenes, Staphylococcus aureaus. (Tetracyclines are not the drugs of choice in the treatment of any type of staphylococcal infections.) • Infections caused by rickettsia including Rocky Mountain spotted fever, typhus group infections, Q fever, rickettsialpox. • Psittacosis caused by Chlamydophila psittaci. • Infections caused by Chlamydia trachomatis such as uncomplicated urethral, endocervical or rectal infections, inclusion conjunctivitis, trachoma, and lymphogranuloma venereum. • Granuloma inquinale caused by Klebsiella granulomatis. • Relapsing fever caused by Borrelia sp. • Bartonellosis caused by Bartonella bacilliformis. • Chancroid caused by Hemophilus ducreyi. • Tularemia caused by Francisella tularensis. • Plaque caused by Yersinia pestis. • Cholera caused by Vibrio cholerae. • Brucellosis caused by Brucella species (tetracycline may be used in conjunction with an aminoglycoside). • Infections due to Campylobacter fetus. • As adjunctive therapy in intestinal amebiasis caused by Entamoeba histolytica. • Urinary tract infections caused by susceptible strains of Escherichia coli, Klebsiella, etc. • Other infections caused by susceptible gram-negative organisms such as E. coli, Enterobacter aerogenes, Shigella sp., Acinetobacter sp., Klebsiella sp., and Bacteroides sp. • In severe acne, adjunctive therapy with tetracycline may be useful. When penicillin is contraindicated, tetracyclines are alternative drugs in the treatment of the following infections: • Syphilis and yaws caused by Treponema pallidum and pertenue, respectively, • Vincent’s infection caused by Fusobacterium fusiforme, • Infections caused by Neisseria gonorrhoeae, • Anthrax caused by Bacillus anthracis, • Infections due to Listeria monocytogenes, • Actinomycosis caused by Actinomyces species, • Infections due to Clostridium species.

Launch Date

1953
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2 μg/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
2.6 μg/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
2.7 μg/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
4.5 μg/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
4.5 μg/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
4.1 μg/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.5 μg/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
27.27 μg × h/mL
300 mg 2 times / day steady-state, oral
dose: 300 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
TETRACYCLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
25.5 μg × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
27 μg × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
31.7 μg × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
55.7 μg × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
56.6 μg × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
74.7 μg × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
26.91 μg × h/mL
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7.2 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
5.6 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
6.2 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: HIGH-FAT
6.7 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
6.1 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
8.1 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
7.85 h
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
TETRACYCLINE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
1000 mg 1 times / day multiple, oral
Recommended
Dose: 1000 mg, 1 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 1 times / day
Sources:
unhealthy, 14 - 35 years
n = 31
Health Status: unhealthy
Condition: acne
Age Group: 14 - 35 years
Sex: M+F
Population Size: 31
Sources:
2.2 |500 mg/mL|mg 2 times / day multiple, topical|oral (complex)
Dose: 2.2 |500 mg/mL|mg, 2 times / day
Route: topical|oral
Route: multiple
Dose: 2.2 |500 mg/mL|mg, 2 times / day
Sources:
unhealthy, 14 - 35 years
n = 36
Health Status: unhealthy
Condition: acne
Age Group: 14 - 35 years
Sex: M+F
Population Size: 36
Sources:
Other AEs: Discoloration skin...
Other AEs:
Discoloration skin
Sources:
250 mg 4 times / day multiple, oral
Recommended
Dose: 250 mg, 4 times / day
Route: oral
Route: multiple
Dose: 250 mg, 4 times / day
Sources:
unhealthy, 38 years
n = 1
Health Status: unhealthy
Condition: pharyngitis
Age Group: 38 years
Sex: M
Population Size: 1
Sources:
Disc. AE: Mucosal ulceration...
AEs leading to
discontinuation/dose reduction:
Mucosal ulceration (1 patient)
Sources:
7 g multiple, intrapleural (total)
Overdose
Dose: 7 g
Route: intrapleural
Route: multiple
Dose: 7 g
Sources:
unhealthy, 41 years
n = 1
Health Status: unhealthy
Age Group: 41 years
Sex: M
Population Size: 1
Sources:
Disc. AE: Pleural disorder...
AEs leading to
discontinuation/dose reduction:
Pleural disorder
Sources:
2 % 2 times / day multiple, intralesional
Dose: 2 %, 2 times / day
Route: intralesional
Route: multiple
Dose: 2 %, 2 times / day
Sources:
unhealthy, 63 years (range: 53–72 years)
n = 21
Health Status: unhealthy
Condition: lower eyelid festoons
Age Group: 63 years (range: 53–72 years)
Sex: M+F
Population Size: 21
Sources:
AEs

AEs

AESignificanceDosePopulation
Discoloration skin
2.2 |500 mg/mL|mg 2 times / day multiple, topical|oral (complex)
Dose: 2.2 |500 mg/mL|mg, 2 times / day
Route: topical|oral
Route: multiple
Dose: 2.2 |500 mg/mL|mg, 2 times / day
Sources:
unhealthy, 14 - 35 years
n = 36
Health Status: unhealthy
Condition: acne
Age Group: 14 - 35 years
Sex: M+F
Population Size: 36
Sources:
Mucosal ulceration 1 patient
Disc. AE
250 mg 4 times / day multiple, oral
Recommended
Dose: 250 mg, 4 times / day
Route: oral
Route: multiple
Dose: 250 mg, 4 times / day
Sources:
unhealthy, 38 years
n = 1
Health Status: unhealthy
Condition: pharyngitis
Age Group: 38 years
Sex: M
Population Size: 1
Sources:
Pleural disorder Disc. AE
7 g multiple, intrapleural (total)
Overdose
Dose: 7 g
Route: intrapleural
Route: multiple
Dose: 7 g
Sources:
unhealthy, 41 years
n = 1
Health Status: unhealthy
Age Group: 41 years
Sex: M
Population Size: 1
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 29 uM]
Drug as victim
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
[Acute nephrosis following enterocolitis due to tetracycline].
1967 Sep 15
Iliacus haematoma syndrome as a complication of anticoagulant therapy.
1968 Oct 12
Polyuric acute renal failure after methoxyflurane and tetracycline.
1971 Dec 11
Protective effect of ascorbic acid, isoascorbic acid and mannitol against tetracycline-induced nephrotoxicity.
1971 Jul
Benign intracranial hypertension. Sequel to tetracycline therapy in a child.
1971 May 31
Benign intracranial hypertension after antibiotic therapy.
1972 Jul 1
Disseminated intravascular coagulation associated with tetracycline-induced hepatorenal failure during pregnancy.
1973 Feb 15
Megaloblastic anemia associated with long-term tetracycline therapy. Report of a case.
1973 Jun
Protein synthesis in Mycobacterium tuberculosis H37Rv and the effect of streptomycin in streptomycin-susceptible and -resistant strains.
1973 Sep
Tetracycline-induced immune hemolytic anemia.
1974 May-Jun
Activity of minocycline and tetracycline against respiratory pathogens related to blood levels.
1975 Sep
The absorption and sputum penetration of doxycycline.
1978 Nov
[Tetracyclin intoxication versus idiopathic pancreatitis: report of a case with multiple organ involvement (author's transl)].
1979
Tetracycline-induced aplastic anemia.
1979 Mar
Drug-induced myocarditis: a report of two cases.
1979 May-Jun
Effect of toxic doses of progesterone on hepatotoxic effects of tetracycline.
1985 Apr
Congenital heart disease in relation to maternal use of Bendectin and other drugs in early pregnancy.
1985 Aug 8
Hemolytic anemia after tetracycline therapy.
1985 Mar 28
Selective absorption of ultraviolet laser energy by human atherosclerotic plaque treated with tetracycline.
1985 May 1
Minor complication of thyroid cyst sclerosis with tetracycline.
1986 Jan
Pseudotumor cerebri--a complication of tetracycline treatment of acne.
1986 Mar
An aborted, prospective, randomized trial of sclerotherapy for prolonged drainage after mastectomy.
1986 May
[Effectiveness of legalon and essentiale in a tetracycline-induced liver lesion].
1986 Oct
Tetracycline sclerotherapy for hydroceles and epididymal cysts.
1987 Apr
Broth microdilution testing of susceptibilities to 30 antimicrobial agents of Mycobacterium avium strains from patients with acquired immune deficiency syndrome.
1987 Oct
Tetracycline-induced renal hypophosphatemia in a patient with a syndrome of inappropriate secretion of antidiuretic hormone.
1988
Pseudotumor cerebri, a rare adverse reaction to tetracycline therapy. A case report.
1988 Dec
Inhibition of HIV-1 RNA-dependent DNA polymerase and cellular DNA polymerases alpha, beta and gamma by phosphonoformic acid and other drugs.
1988 Feb
Continuous thoracic epidural analgesia for the control of pain associated with pleural sclerosis.
1989 Jan
Combination chemotherapy for primary small intestinal lymphoma in the Middle East.
1989 May
Anosmia after doxycycline use.
1990 Apr 16
Protective activity of tetracycline analogs against the cytopathic effect of the human immunodeficiency viruses in CEM cells.
1990 Jan-Feb
In vitro and in vivo effects of doxycycline on Toxoplasma gondii.
1990 May
Protective effect of bicyclol on tetracycline-induced fatty liver in mice.
2009 Jul 10
Gel entrapment culture of rat hepatocytes for investigation of tetracycline-induced toxicity.
2009 Jul 15
Decreased nanobacteria levels and symptoms of nanobacteria-associated interstitial cystitis/painful bladder syndrome after tetracycline treatment.
2010 Jan
Epidural abscess caused by community-associated methicillin-resistant Staphylococcus aureus strain USA300 in Japan.
2010 Oct
Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature.
2010 Sep
Synergistic drug combinations for tuberculosis therapy identified by a novel high-throughput screen.
2011 Aug
Fluorocyclines. 1. 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline: a potent, broad spectrum antibacterial agent.
2012 Jan 26
Development of a multiparametric cell-based protocol to screen and classify the hepatotoxicity potential of drugs.
2012 May
Effect of ribosome-targeting antibiotics on streptomycin-resistant Mycobacterium mutants in the rpsL gene.
2013 Aug
Old drug, new target: ellipticines selectively inhibit RNA polymerase I transcription.
2013 Feb 15
Evaluation of aggregating brain cell cultures for the detection of acute organ-specific toxicity.
2013 Jun
Model steatogenic compounds (amiodarone, valproic acid, and tetracycline) alter lipid metabolism by different mechanisms in mouse liver slices.
2014
A simple transcriptomic signature able to predict drug-induced hepatic steatosis.
2014 Apr
Mechanisms of amiodarone and valproic acid induced liver steatosis in mouse in vivo act as a template for other hepatotoxicity models.
2014 Aug
Gene expression markers in the zebrafish embryo reflect a hepatotoxic response in animal models and humans.
2014 Oct 1
Multiparametric assay using HepaRG cells for predicting drug-induced liver injury.
2015 Jul 2
Increased hepatic Fatty Acid uptake and esterification contribute to tetracycline-induced steatosis in mice.
2015 Jun
Patents

Sample Use Guides

TETRACYCLINE HYDROCHLORIDE - tetracycline hydrochloride capsule Adults: Usual daily dose, 1 gram as 500 mg twice a day or 250 mg four times a day. Higher doses such as 500 mg four times a day may be required for severe infections or for those infections which do not respond to the smaller doses. For pediatric patients above eight years of age: Usual daily dose, 10 mg/lb to 20 mg/lb (25mg/kg to 50 mg/kg) body weight divided in four equal doses. TETRACYCLINE VISION 10 mg/g eye ointment Adults and children: depending on the severity of condition, a strip of the eye ointment with length of 1 – 1.5 cm is inserted into the conjunctival fold of the lower eyelid 3 - 4 times daily and in more severe cases, up to 6 times daily.
Route of Administration: Other
Standard tetracycline powders should provide the following range of Minimal Inhibitory Concentration values: Enterococcus faecalis ATCC 29212 8 - 32 mcg/mL Escherichia coli ATCC 25922 0.5 - 2 mcg/mL Haemophilus influenzae ATCC 49247 4 - 32 mcg/mL Mycoplasma pneumoniae ATCC 29342 0.06-0.5 mcg/mL Staphylococcus aureus ATCC 29213 0.12 - 1 mcg/mL Streptococcus pneumoniae ATCC 49619 0.06 - 0.5 mcg/mL
Substance Class Chemical
Created
by admin
on Sat Dec 16 10:08:28 GMT 2023
Edited
by admin
on Sat Dec 16 10:08:28 GMT 2023
Record UNII
93V6NC52SB
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TETRACYCLINE TRIHYDRATE
MI   WHO-DD  
Common Name English
Tetracycline trihydrate [WHO-DD]
Common Name English
2-NAPHTHACENECARBOXAMIDE, 4-(DIMETHYLAMINO)-1,4,4A,5,5A,6,11,12A-OCTAHYDRO-3,6,10,12,12A-PENTAHYDROXY-6-METHYL-1,11-DIOXO-, HYDRATE (1:3), (4S,4AS,5AS,6S,12AS)-
Systematic Name English
TETRACYCLINE TRIHYDRATE [MI]
Common Name English
Code System Code Type Description
SMS_ID
100000163639
Created by admin on Sat Dec 16 10:08:28 GMT 2023 , Edited by admin on Sat Dec 16 10:08:28 GMT 2023
PRIMARY
FDA UNII
93V6NC52SB
Created by admin on Sat Dec 16 10:08:28 GMT 2023 , Edited by admin on Sat Dec 16 10:08:28 GMT 2023
PRIMARY
EVMPD
SUB178043
Created by admin on Sat Dec 16 10:08:28 GMT 2023 , Edited by admin on Sat Dec 16 10:08:28 GMT 2023
PRIMARY
CAS
6416-04-2
Created by admin on Sat Dec 16 10:08:28 GMT 2023 , Edited by admin on Sat Dec 16 10:08:28 GMT 2023
PRIMARY
RXCUI
236873
Created by admin on Sat Dec 16 10:08:28 GMT 2023 , Edited by admin on Sat Dec 16 10:08:28 GMT 2023
PRIMARY RxNorm
PUBCHEM
67858637
Created by admin on Sat Dec 16 10:08:28 GMT 2023 , Edited by admin on Sat Dec 16 10:08:28 GMT 2023
PRIMARY
Related Record Type Details
ANHYDROUS->SOLVATE