Details
Stereochemistry | ACHIRAL |
Molecular Formula | C10H13NO2 |
Molecular Weight | 179.2157 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CCOC1=CC=C(NC(C)=O)C=C1
InChI
InChIKey=CPJSUEIXXCENMM-UHFFFAOYSA-N
InChI=1S/C10H13NO2/c1-3-13-10-6-4-9(5-7-10)11-8(2)12/h4-7H,3H2,1-2H3,(H,11,12)
Molecular Formula | C10H13NO2 |
Molecular Weight | 179.2157 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
DescriptionSources: https://www.ncbi.nlm.nih.gov/books/NBK304337Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18140117 | https://www.ncbi.nlm.nih.gov/pubmed/3552585 | https://www.ncbi.nlm.nih.gov/pubmed/12242329 | https://www.ncbi.nlm.nih.gov/pubmed/14592552
Sources: https://www.ncbi.nlm.nih.gov/books/NBK304337
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18140117 | https://www.ncbi.nlm.nih.gov/pubmed/3552585 | https://www.ncbi.nlm.nih.gov/pubmed/12242329 | https://www.ncbi.nlm.nih.gov/pubmed/14592552
Phenacetin was used as an analgesic and fever-reducing drug in both human and veterinary medicine for many years. Since a major portion of a dose of phenacetin is rapidly metabolised to paracetamol, it seems possible that phenacetin owes some of its therapeutic activity to its main metabolite, paracetamol, whereas its most troublesome side effect (methaemoglobinaemia) is due to another metabolite, p-phenetidine.
Phenacetin was shown to inhibit cyclooxygenase (COX)-3, a cyclooxygenase-1 variant while p-phenetidine potently inhibits both COX-1 and COX-2. There is sufficient evidence in humans for the carcinogenicity of analgesic mixtures containing phenacetin. Analgesic mixtures containing phenacetin cause cancer of the renal pelvis, and of the ureter. Phenacetin was withdrawn from many analgesic mixtures long before the legal ban in several countries.
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: Q8HZR1 Gene ID: 403544.0 Gene Symbol: PTGS1 Target Organism: Canis lupus familiaris (Dog) (Canis familiaris) Sources: https://www.ncbi.nlm.nih.gov/pubmed/12242329 |
102.0 µM [IC50] | ||
Target ID: CHEMBL221 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14592552 |
|||
Target ID: CHEMBL230 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14592552 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Phenacetin Approved UsePhenacetin was used as an analgesic and fever-reducing drug in both human and veterinary medicine for many years. Launch Date1886 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
6.9 μg/mL |
900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered: |
ACETAMINOPHEN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
13.5 μg/mL |
1.5 g single, oral dose: 1.5 g route of administration: Oral experiment type: SINGLE co-administered: |
PHENACETIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1.48 μg/mL |
900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered: |
PHENACETIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1.84 μg/mL |
900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered: |
PHENACETIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
2.5 μg/mL |
900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered: |
PHENACETIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
40.4 μg × h/mL |
900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered: |
ACETAMINOPHEN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
20.72 μg × h/mL |
1.5 g single, oral dose: 1.5 g route of administration: Oral experiment type: SINGLE co-administered: |
PHENACETIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1.58 μg × h/mL |
900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered: |
PHENACETIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1.84 μg × h/mL |
900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered: |
PHENACETIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
5.3 μg × h/mL |
900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered: |
PHENACETIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2.6 h |
900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered: |
ACETAMINOPHEN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
0.6 h |
1.5 g single, oral dose: 1.5 g route of administration: Oral experiment type: SINGLE co-administered: |
PHENACETIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
0.98 h |
900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered: |
PHENACETIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
1.1 h |
900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered: |
PHENACETIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
|
0.9 h |
900 mg single, oral dose: 900 mg route of administration: Oral experiment type: SINGLE co-administered: |
PHENACETIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
70% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23607050/ |
PHENACETIN plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
1.5 g 1 times / day multiple, oral Studied dose Dose: 1.5 g, 1 times / day Route: oral Route: multiple Dose: 1.5 g, 1 times / day Sources: |
unhealthy, 34 years n = 1 Health Status: unhealthy Condition: migraine Age Group: 34 years Sex: F Population Size: 1 Sources: |
Other AEs: Nephropathy... |
250 mg multiple, oral Studied dose Dose: 250 mg Route: oral Route: multiple Dose: 250 mg Co-administed with:: acetylsalicylic acid(250 mg; 40 years) Sources: codeine phosphate(10 mg; 40 years) |
unhealthy, 54 years n = 1 Health Status: unhealthy Condition: migraine Age Group: 54 years Sex: F Population Size: 1 Sources: |
Other AEs: Nephropathy... |
1 g 1 times / day multiple, oral Studied dose Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: |
unhealthy, 56 years n = 1 Health Status: unhealthy Condition: knee pain Age Group: 56 years Sex: M Population Size: 1 Sources: |
Other AEs: Transitional cell carcinoma... |
625 mg 1 times / day multiple, oral (mean) Studied dose Dose: 625 mg, 1 times / day Route: oral Route: multiple Dose: 625 mg, 1 times / day Sources: |
unhealthy, 85 years n = 1 Health Status: unhealthy Condition: migraine Age Group: 85 years Sex: M Population Size: 1 Sources: |
Other AEs: Urothelial carcinoma... |
0.9 g 4 times / day multiple, oral Studied dose Dose: 0.9 g, 4 times / day Route: oral Route: multiple Dose: 0.9 g, 4 times / day Sources: |
healthy, age 18 to 44 years n = 10 Health Status: healthy Age Group: age 18 to 44 years Sex: M+F Population Size: 10 Sources: |
Other AEs: Nephritis NEC... |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Nephropathy | 1.5 g 1 times / day multiple, oral Studied dose Dose: 1.5 g, 1 times / day Route: oral Route: multiple Dose: 1.5 g, 1 times / day Sources: |
unhealthy, 34 years n = 1 Health Status: unhealthy Condition: migraine Age Group: 34 years Sex: F Population Size: 1 Sources: |
|
Nephropathy | 250 mg multiple, oral Studied dose Dose: 250 mg Route: oral Route: multiple Dose: 250 mg Co-administed with:: acetylsalicylic acid(250 mg; 40 years) Sources: codeine phosphate(10 mg; 40 years) |
unhealthy, 54 years n = 1 Health Status: unhealthy Condition: migraine Age Group: 54 years Sex: F Population Size: 1 Sources: |
|
Transitional cell carcinoma | 1 g 1 times / day multiple, oral Studied dose Dose: 1 g, 1 times / day Route: oral Route: multiple Dose: 1 g, 1 times / day Sources: |
unhealthy, 56 years n = 1 Health Status: unhealthy Condition: knee pain Age Group: 56 years Sex: M Population Size: 1 Sources: |
|
Urothelial carcinoma | 625 mg 1 times / day multiple, oral (mean) Studied dose Dose: 625 mg, 1 times / day Route: oral Route: multiple Dose: 625 mg, 1 times / day Sources: |
unhealthy, 85 years n = 1 Health Status: unhealthy Condition: migraine Age Group: 85 years Sex: M Population Size: 1 Sources: |
|
Nephritis NEC | 20% | 0.9 g 4 times / day multiple, oral Studied dose Dose: 0.9 g, 4 times / day Route: oral Route: multiple Dose: 0.9 g, 4 times / day Sources: |
healthy, age 18 to 44 years n = 10 Health Status: healthy Age Group: age 18 to 44 years Sex: M+F Population Size: 10 Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/10421611/ Page: 1.0 |
inconclusive | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10421611/ Page: 1.0 |
inconclusive | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10421611/ Page: 1.0 |
inconclusive | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10421611/ Page: 1.0 |
inconclusive | |||
Page: 1.0 |
major | yes (co-administration study) Comment: cigarette smoking induced CYP1A2 and increased O-deethylase activity Page: 1.0 |
||
Sources: https://pubmed.ncbi.nlm.nih.gov/10627170/ Page: 1.0 |
minor | |||
Sources: https://pubmed.ncbi.nlm.nih.gov/10421611/ Page: 1.0 |
minor |
PubMed
Title | Date | PubMed |
---|---|---|
Letter: The clinical course of patients with analgesic nephropathy. | 1975 Aug 9 |
|
The induction of renal papillary necrosis in Gunn rats by analgesics and analgesic mixtures. | 1975 Feb |
|
The radiological diagnosis of analgesic nephropathy. | 1975 Jul |
|
Role of CYP1A2 in the toxicity of long-term phenacetin feeding in mice. | 1999 Jul |
|
Epidemiology and etiology of premalignant and malignant urothelial changes. | 2000 |
|
Neonatal mouse model: review of methods and results. | 2001 |
|
Xpa and Xpa/p53+/- knockout mice: overview of available data. | 2001 |
|
[Determination of three components in compound chlorophenamine tablet by iterative target transformation factor analysis]. | 2001 Apr |
|
Relationship between nonphenacetin-combined analgesics and nephropathy. | 2001 Jun |
|
Relationship between nonphenacetin-combined analgesics and nephropathy. | 2001 Jun |
|
Relationship between nonphenacetin-combined analgesics and nephropathy. | 2001 Jun |
|
Suppression of agglomeration in fluidized bed coating. IV. Effects of sodium citrate concentration on the suppression of particle agglomeration and the physical properties of HPMC film. | 2001 Mar 14 |
|
Optimization of an exogenous metabolic activation system for FETAX. II. Preliminary evaluation. | 2001 May |
|
Retrospective analysis of drug-induced urticaria and angioedema: a survey of 2287 patients. | 2001 Nov |
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Review of potential risk factors for kidney (renal cell) cancer. | 2001 Nov |
|
Relationship between nonphenacetin combined analgesics and nephropathy. | 2001 Nov |
|
Fondaparinux sodium is not metabolised in mammalian liver fractions and does not inhibit cytochrome P450-mediated metabolism of concomitant drugs. | 2002 |
|
Decreased hepatic drug metabolising enzyme activity in rats with nitrosamine-induced tumours. | 2002 |
|
In vivo effect of diallyl sulfide and cimetidine on phenacetin metabolism and bioavailability in rat. | 2002 |
|
Comparison of vasoconstrictor responses to selected NSAIDs in rabbit renal and femoral arteries. | 2002 |
|
The onset of action and the analgesic efficacy of Saridon (a propyphenazone/paracetamol/ caffeine combination) in comparison with paracetamol, ibuprofen, aspirin and placebo (pooled statistical analysis). | 2002 |
|
Phenacetin O-deethylation in extrahepatic tissues of rats. | 2002 Apr-Jun |
|
Prediction of hepatic clearance and availability by cryopreserved human hepatocytes: an application of serum incubation method. | 2002 Aug |
|
Evaluation of cytochrome P450 probe substrates commonly used by the pharmaceutical industry to study in vitro drug interactions. | 2002 Dec |
|
[Simultaneous determination of four components in the compound child phenobarbital tablet using ultraviolet spectrophotometry]. | 2002 Feb 28 |
|
Evaluation of the surfactant properties of ascorbyl palmitate sodium salt. | 2002 Jul |
|
Substrate specificity for rat cytochrome P450 (CYP) isoforms: screening with cDNA-expressed systems of the rat. | 2002 Mar 1 |
|
Use of analgesics in self-medication. | 2002 Mar-Apr |
|
[A case of renal pelvic tumor due to phenacetin abuse]. | 2002 May |
|
Hydrogen bonding with adsorbent during storage governs drug dissolution from solid-dispersion granules. | 2002 Nov |
|
Interactions of human organic anion transporters and human organic cation transporters with nonsteroidal anti-inflammatory drugs. | 2002 Nov |
|
Phenotype of CYP2C19 and CYP3A4 by determination of omeprazole and its two main metabolites in plasma using liquid chromatography with liquid-liquid extraction. | 2002 Nov 25 |
|
Monolithic silica rod liquid chromatography with ultraviolet or fluorescence detection for metabolite analysis of cytochrome P450 marker reactions. | 2002 Nov 25 |
|
Hospitalized poisonings after renal transplantation in the United States. | 2002 Nov 26 |
|
COX-3, a cyclooxygenase-1 variant inhibited by acetaminophen and other analgesic/antipyretic drugs: cloning, structure, and expression. | 2002 Oct 15 |
|
Polymer particle erosion controlling drug release. II. Swelling investigations to clarify the release mechanism. | 2002 Oct 24 |
|
Correlation between induction of DNA fragmentation in urinary bladder cells from rats and humans and tissue-specific carcinogenic activity. | 2002 Sep 30 |
|
Analgesics and renal disease in the postphenacetin era. | 2003 Aug |
|
Identification of cytochrome P450 1A2 as enzyme involved in the microsomal metabolism of Huperzine A. | 2003 Feb 14 |
|
High-throughput inhibition screening of major human cytochrome P450 enzymes using an in vitro cocktail and liquid chromatography-tandem mass spectrometry. | 2003 Jan 1 |
|
Simultaneous liquid chromatography-tandem mass spectrometric determination of albendazole sulfoxide and albendazole sulfone in plasma. | 2003 Jan 5 |
|
Cytochrome P450 inhibition using recombinant proteins and mass spectrometry/multiple reaction monitoring technology in a cassette incubation. | 2003 Jul |
|
Effects of phenacetin and its metabolite p-phenetidine on COX-1 and COX-2 activities and expression in vitro. | 2003 Jun 15 |
|
Mechanism-based inhibition of human liver microsomal cytochrome P450 1A2 by zileuton, a 5-lipoxygenase inhibitor. | 2003 Nov |
|
Effects of non-steroidal anti-inflammatory drugs on cancer sites other than the colon and rectum: a meta-analysis. | 2003 Oct 31 |
|
HPLC analyses and pharmacokinetic studies of baicalin and oxymatrine in rabbits. | 2003 Sep |
|
Assessment of tableting properties using infinitesimal quantities of powdered medicine. | 2003 Sep 16 |
|
Atomoxetine hydrochloride: clinical drug-drug interaction prediction and outcome. | 2004 Feb |
|
In vitro metabolism and inductive or inhibitive effect of DL111 on rat cytochrome P4501A enzyme. | 2004 Mar 15 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/books/NBK304337/
Analgesic mixtures containing phenacetin were previously marketed as tablets or capsules containing between 150 and 300 mg phenacetin. Common combinations were: 150 mg phenacetin, 230 mg aspirin, and 15 or 30 mg caffeine; or 150 mg phenacetin, 230 mg aspirin, 30 mg caffeine, and 8, 15, 30, or 60 mg codeine phosphate. Phenacetin alone was also available in 250 and 300 mg doses as tablets, and up to 500 mg doses as powder. The usual dose was 300 mg 4–6 times per day, and the daily dose was not to exceed 2 g
Route of Administration:
Oral
Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:05:26 GMT 2023
by
admin
on
Fri Dec 15 15:05:26 GMT 2023
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Record UNII |
ER0CTH01H9
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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WHO-ATC |
N02BE53
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WHO-VATC |
QN02BE53
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WHO-ATC |
N02BE03
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WHO-VATC |
QN02BE73
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IARC | Phenacetin | ||
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WHO-ATC |
N02BE73
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NCI_THESAURUS |
C45176
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WHO-VATC |
QN02BE03
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SUB09745MIG
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7402
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62-44-2
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8050
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ER0CTH01H9
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1514008
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7651
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412
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C44432
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ER0CTH01H9
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2115
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PHENACETIN
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3152
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8113
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CHEMBL16073
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D010615
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DB03783
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m8589
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PRIMARY | Merck Index | ||
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100000088566
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200-533-0
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4754
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Related Record | Type | Details | ||
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METABOLIC ENZYME -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR |
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METABOLIC ENZYME -> SUBSTRATE |
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Related Record | Type | Details | ||
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METABOLITE TOXIC -> PARENT |
Metabolite induced methaemoglobinaemia in man.
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METABOLITE ACTIVE -> PARENT |
Percent of dose excreted in urine as metabolite.
AMOUNT ADMINISTERED
URINE
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METABOLITE ACTIVE -> PARENT |
Metabolite to parent drug ratio in non-uraemic human plasma.
METABOLITE TO PARENT DRUG RATIO
PLASMA; URINE
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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