Download Clofibric acid

Clofibric acid
Chemical structure:
CH3
Cl
O
O C C
OH
CH3
Chemical formula: C10H11O3Cl
IUPAC name: 2-(4-chlorophenoxy)-2-methyl propionic acid
CAS No: 882-09-7
Appliances: Clofibric acid is an active metabolite of clofibrate, etofibrate and etofyllinclofibrate which
are drugs used as blood lipid regulators. These substances are used to decrease the plasmatic concentration of cholesterol and triglycerides. The mechanism of action has not been established definitively.
Dosage and administration: Patients ingest one capsule (500 mg) of clofibrate one to four times
per day.
Metabolism and elimination (http://www.rxlist.com/cgi/generic2/clofibrate.htm): After an oral administration, Clofibrate is quickly and completely reduced of the gastro-intestinal tract and is degraded by
hydrolysis in clofibric acid. Between 95% and 99% of an oral dose of clofibrate is excreted in the
urine as free and conjugated clofibric acid.
Etofyllinclofibrate is well reduced after oral administration. It is not found in the blood under unchanged shape, but under the shape of its two main metabolites: etofylline and clofibric acid. The
half-life of elimination is about 12-18 hours. Eight hours after the administration, 8,5 % of the dose
are eliminated in urine in the form of clofibric acid.
Medicines on sale in Switzerland: Clofibrat Tripharma®, Lipo-Merz®retard, Duolip®
Data on consumption: t (Schweiz)
Physical chemical properties:
Water solubility
Partition coefficient octanol/water (log Kow)
Vapor pressure (20 °C)
Organic carbon-water partition coefficient (Koc)
Ocurrence in the environment:
Clofibric acid has already been detected in STP effluents at concentrations up to 1600 ng/l (Stumpf et
al., 1996). In the aquatic environment, it was detected in German river waters at concentrations up to
550 ng/l (Ternes, 1998) and in Swiss lakes at concentrations up to 9 ng/l (Buser et al., 1998). It was
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even found in samples of ground water wells at a drinking water treatment plant (up to 7300 ng/l)
(Heberer et al., 1997).
Ecotoxicity:
EC50
Daphnia magna
106 mg/L
48h EC50
Zebrafish (Brachydanio rerio)
86 mg/L
72h EC50
Algae (Scenedesmus subspicatus)
89 mg/L
Toxicity:
Carcinogenesis (http://www.rxlist.com/cgi/generic2/clofibrate.htm)
Administration of clofibrate to mice and rats in long-term studies at 1 to 2 times the maximum
recommended human dose (based on surface area, mg/m2 ), resulted in a higher incidence of
benign and malignant liver tumors than in controls. There was an increase in benign Leydig cell
tumors in male rats treated at 400 mg/kg/day or 2 times the maximum recommended human dose in
one study. A comparative carcinogenicity study was also done in rats comparing three drugs in this
class: fenofibrate (10 and 60 mg/kg; 0.3 and 1.6 times the human dose), clofibrate (400 mg/kg; 1.6
times the human dose), and gemfibrozil (250 mg/kg; 1.7 times the human dose). Pancreatic acinar
adenomas were increased in males and females on fenofibrate; hepatocellular carcinoma and
pancreatic acinar adenomas were increased in males and hepatic neoplastic nodules in females
treated with clofibrate; hepatic neoplastic nodules were increased in males and females treated with
gemfibrozil while testicular interstitial cell tumors were increased in males on all three drugs.
Impairment of fertility (http://www.rxlist.com/cgi/generic2/clofibrate.htm)
Arrest of spermatogenesis has been seen in both dogs and monkeys at doses approximately 2 times
the maximum recommended human dose (based on surface area).
Adverse effects on human
The treatment with these drugs can result in some gastro-intestinal confusions, such as sickness,
vomit and diarrhoea. Very rare cases of fall of hair, impotence and muscular pains were reported.
Diseases of bile tract can arise following a long treatment with blood lipid regulators.
Data on degradation:
References:
Buser H. R., Muller M. D. and Theobald N. Occurrence of the pharmaceutical drug clofibric acid and
the herbicide mecoprop in various Swiss lakes and in the North Sea. Environmental Science & Technology, 1998, vol. 32, n° 1, p. 188-192.
Heberer T., Dünnbier U., Reilich C. and Stan H.-J. Detection of drugs and drug metabolites in ground
water samples of a drinking water treatment plant. Fresenius Environmental Bulletin, 1997, vol. 6, p.
438-443.
Stumpf M., Ternes T. A., Haberer K., Seel P. and Baumann W. Determination of pharmaceutics in
sewage plants and river water. Vom Wasser, 1996, vol. 86, p. 291-303.
Ternes T. A. Occurrence of drugs in german sewage treatment plants and rivers. Water Research,
1998, vol. 32, n° 11, p. 3245-3260.
Webb S. F. A Data-based Perspective on the environmental Risk Assessment of Human Pharmaceuticals I - Collation of Available Ecotoxicity Data. In Pharmaceutical in the Environment: Sources, fate,
effects and risks, K. Kümmerer Ed., Berlin Heidelberger New York: Springer, 2001.
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Diclofenac
Chemical structure:
O
C
H2C
OH(Na)
Cl
N
H
Cl
Chemical formula: C14H10Cl2NNaO2
IUPAC name: 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid
CAS No: 15307-86-5
Appliances: Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID). In pharmacologic studies,
diclofenac has shown anti-inflammatory, analgesic, and antipyretic activity. As with other NSAIDs, its
mode of action is not known.
Dosage and administration (http://www.rxlist.com/cgi/generic/diclofen.htm): Diclofenac is indicated
for the acute and chronic treatment of signs and symptoms of osteoarthritis and rheumatoid arthritis.
In addition, diclofenac are indicated for the treatment of ankylosing spondylitis and for the management of pain and primary dysmenorrhea. Diclofenac may be administered from 25 to 75mg.
Metabolism and elimination (http://www.rxlist.com/cgi/generic/diclofen.htm): Diclofenac is
eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and
the sulfate conjugates of the metabolites. Approximately 65% of the dose is excreted in the urine,
and approximately 35% in the bile. Conjugates of unchanged diclofenac account for 5%-10% of the
dose excreted in the urine and for less than 5% excreted in the bile. Little or no unchanged unconjugated drug is excreted. Conjugates of the principal metabolite account for 20%-30% of the dose excreted in the urine and for 10%-20% of the dose excreted in the bile. Conjugates of three other metabolites together account for 10%-20% of the dose excreted in the urine and for small amounts excreted in the bile. Some of the metabolites may have activity.
Medicines on sale in Switzerland: Inflama®, Voltaren, Olfen®, etc
Data on consumption: t (Switzerland)
Physical chemical properties:
Solubility in MeOH/water
7760 mg/L<
Partition coefficient octanol/water (log Kow)
13.4 at pH 7.4 and 1545 at pH 5.2
Vapor pressure (25 °C)
4.0 ± 0.2
Organic carbon-water partition coefficient (Koc)
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Ocurrence in the environment:
Diclofenac was already detected in surface waters and sewage treatment plant at maximum concentrations of 1200 ng/l and 2100 ng/l respectively (Buser et al., 1998; Stumpf et al., 1999; Ternes,
1998).
Ecotoxicity:
No data available
Toxicity:
Animal toxicity (Merck index)
LD50
Oral mice
390 mg/kg
LD50
Oral rat
150 mg/kg
Adverse effects on human (http://www.rxlist.com/cgi/generic/diclofen.htm)
Incidence greater than 1% : Abdominal pain or cramps, headache, fluid retention, abdominal distention. Digestive perturbation (diarrhoea, indigestion, nausea, constipation, flatulence, liver test abnormalities, peptic ulcer, with or without bleeding and/or perforation, or bleeding without ulcer). Effect on
nervous system (dizziness) etc.
Data on degradation:
References:
Buser H. R., Poiger T. and Muller M. D. Occurrence and fate of the pharmaceutical drug diclofenac in
surface waters: Rapid photodegradation in a lake. Environmental Science & Technology, 1998, vol.
32, n° 22, p. 3449-3456.
Stumpf M., Ternes T. A., Wilken R. D., Rodrigues S. V. and Baumann W. Polar drug residues in
sewage and natural waters in the state of Rio de Janeiro, Brazil. The Science of the Total Environment, 1999, vol. 225, n° 1-2, p. 135-141.
Ternes T. A. Occurrence of drugs in german sewage treatment plants and rivers. Water Research,
1998, vol. 32, n° 11, p. 3245-3260.
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Diclofenac
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Ibuprofen
Chemical structure:
H3C
CH3
CH C
H2
H3C
C
H
O
C
OH
Chemical formula: C13H18O2
IUPAC name: 2-(4-isobutylphenyl)propionic acid
CAS No: 15687-27-1
Appliances: Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID). Ibuprofen possesses analgesic and antipyretic activities. As with other NSAIDs, its mode of action is not known. It is one of the
most important pharmaceuticals in term of quantities consumed.
Dosage and administration (http://www.rxlist.com/cgi/generic/ibup.htm): Ibuprofen is indicated for
relief of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Ibuprofen is also indicated
for relief of mild to moderate pain and for the treatment of primary dysmenorrhea. The suggested
dosage is 1200 -3200 mg daily, and do not exceed 3200 mg total daily dose.
Metabolism and elimination (http://www.rxlist.com/cgi/generic/ibup.htm): Ibuprofen is rapidly absorbed when administered orally. Studies have shown that following ingestion of the drug, 45% to
79% of the dose was recovered in the urine within 24 hours as metabolite A (25%), (+)-2-4’-(2hydroxy-2-methylpropyl)-phenylpropionic acid and metabolite B (37%), (+)-2-4’-(2-carboxypropyl)phenylpropionic acid; the percentages of free and conjugated ibuprofen were approximately 1% and
14%, respectively.
Medicines on sale in Switzerland: Algifor®, Dolocyl®, Ecoprofen®, etc.
Data on consumption: t (Switzerland)
Physical chemical properties:
Solubility in MeOH/water (1/99)
83 mg/L
Partition coefficient octanol/water (log Kow)
-
Vapor pressure (20 °C)
-
Organic carbon-water partition coefficient (Koc)
Ocurrence in the environment:
Ibuprofen was already detected in surface waters and sewage treatment plants at maximum concentrations of 530 ng/l and 3400 ng/l respectively (Buser et al., 1998; Stumpf et al., 1999; Ternes, 1998).
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Ecotoxicity:
48h EC50
Daphnia magna
9.1 mg/L
96h EC50
Bluegill sunfis (Lepomis macrochirus)
173 mg/L
96h EC50
Diatom (Skeletonema costatum)
7.1 mg/L
Toxicity:
Animal toxicity (Merck index)
LD50
Oral, mice
1255 mg/kg
LD50
i.p., mice
495 mg/kg
LD50
Oral rat
1050 mg/kg
LD50
i.p. rat
626 mg/kg
Adverse effects on human (http://www.rxlist.com/cgi/generic/ibup.htm)
The most frequent type of adverse reaction occurring with ibuprofen is gastrointestinal (Nausea, epigastric pain, heartburn, diarrhoea, abdominal distress, nausea and vomiting, indigestion, constipation, abdominal cramps or pain). Adverse reactions observed during controlled clinical trials at an incidence greater than 1% are effects on central nervous system (dizziness, headache, nervousness)
and dermatologic effect (rash, pruritus).
Data on degradation:
References:
Buser H. R., Poiger T. and Muller M. D. Occurrence and fate of the pharmaceutical drug diclofenac in
surface waters: Rapid photodegradation in a lake. Environmental Science & Technology, 1998, vol.
32, n° 22, p. 3449-3456.
Stumpf M., Ternes T. A., Wilken R. D., Rodrigues S. V. and Baumann W. Polar drug residues in
sewage and natural waters in the state of Rio de Janeiro, Brazil. The Science of the Total Environment, 1999, vol. 225, n° 1-2, p. 135-141.
Ternes T. A. Occurrence of drugs in german sewage treatment plants and rivers. Water Research,
1998, vol. 32, n° 11, p. 3245-3260.
Webb S. F. A Data-based Perspective on the environmental Risk Assessment of Human Pharmaceuticals I - Collation of Available Ecotoxicity Data. In Pharmaceutical in the Environment: Sources, fate,
effects and risks, K. Kümmerer Ed., Berlin Heidelberger New York: Springer, 2001.
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Ibuprofen
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Ketoprofen
Chemical structure:
CH3
CH
O
C
OH
C
O
Chemical formula: C16H14O3
IUPAC name: 2-(meta-Benzoylphenyl) propionic acid
CAS No: 22071-15-4
Appliances: Ketoprofen is a nonsteroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. As with other NSAIDs, its mode of action is not known.
Dosage and administration (http://www.rxlist.com/cgi/generic/ketoprof.htm): Ketoprofen is indicated
for the management of the signs and symptoms of rheumatoid arthritis and osteoarthritis. Ketoprofen
is indicated for the management of pain and for treatment of primary dysmenorrhea. The recommended starting dose of ketoprofen in otherwise healthy patients is 75 mg three times or 50 mg four
times a day or 200 mg administered once a day. The recommended maximum daily dose of ketoprofen is 200-300 mg/day.
Metabolism and elimination (http://www.rxlist.com/cgi/generic/ketoprof.htm): The metabolic fate of
ketoprofen is glucuronide conjugation to form an unstable acyl-glucuronide. The glucuronic acid
moiety can be converted back to the parent compound. There are unknown active metabolites of ketoprofen. It has been shown not to induce drug-metabolizing enzymes. In a 24-hour period,
approximately 80% of an administered dose of ketoprofen is excreted in the urine, primarily as the
glucuronide metabolite.
Medicines on sale in Switzerland: Fastum®
Data on consumption: t (Switzerland)
Physical chemical properties:
Solubility in MeOH/water (1/99)
220 mg/L
Solubility in water at pH 7
0.3 mg/L
Partition coefficient octanol/water (log Kow)
Vapor pressure (20 °C)
Organic carbon-water partition coefficient (Koc)
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Ocurrence in the environment:
Ketoprofen is detected in surface waters and sewage treatment plants of 120 ng/l and 380 ng/l respectively (Stumpf et al., 1996; Stumpf et al., 1999; Ternes, 1998).
Ecotoxicity:
No data available
Toxicity:
Animal toxicity (Merck index)
LD50
Oral, mice
101 mg/kg
Carcinogenesis, mutagenesis, impairment of fertility (http://www.rxlist.com/cgi/generic/ketoprof.htm)
Chronic oral toxicity studies in mice (up to 32 mg/kg/day; 96 mg/m2/day) did not indicate a carcinogenic potential for ketoprofen. A 2-year carcinogenicity study in rats, using doses up to 6.0 mg/kg/day
(36 mg/m2/day), showed no evidence of tumorigenic potential. Abnormal spermatogenesis or inhibition of spermatogenesis developed in rats and dogs at high doses, and a decrease in the weight of
the testes occurred in dogs and baboons at high doses.
Impairment of fertility (http://www.rxlist.com/cgi/generic2/clofibrate.htm)
Arrest of spermatogenesis has been seen in both dogs and monkeys at doses approximately 2 times
the maximum recommended human dose (based on surface area).
Adverse effects on human (http://www.rxlist.com/cgi/generic/ketoprof.htm)
The most frequent type of adverse reaction occurring with ketoprofen is gastrointestinal (nausea, abdominal pain, diarrhea, constipation, flatulence, anorexia, vomiting). Adverse reactions observed during controlled clinical trials at an incidence greater than 1% are effects on central nervous system
(dizziness, headache, excitation) and dermatologic effect (rash).Very rare cases of fall of hair, impotence and muscular pains were reported.
Data on degradation:
References:
Stumpf M., Ternes T. A., Haberer K., Seel P. and Baumann W. Determination of pharmaceutics in
sewage plants and river water. Vom Wasser, 1996, vol. 86, p. 291-303.
Stumpf M., Ternes T. A., Wilken R. D., Rodrigues S. V. and Baumann W. Polar drug residues in
sewage and natural waters in the state of Rio de Janeiro, Brazil. The Science of the Total Environment, 1999, vol. 225, n° 1-2, p. 135-141.
Ternes T. A. Occurrence of drugs in german sewage treatment plants and rivers. Water Research,
1998, vol. 32, n° 11, p. 3245-3260.
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Ketoprofen
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Mefenamic acid
Chemical structure:
O
C
OH
N
H
H3C
CH 3
Chemical formula: C15H15NO2
IUPAC name: N-(2,3-Xylyl)anthranilic acid
CAS No: 61-68-7
Appliances: Mefenamic acid is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits antiinflammatory, analgesic, and antipyretic activities. The mechanism of action of mefenamic acid, like
that of other NSAIDs, is not completely understood.
Dosage and administration (http://www.rxlist.com/cgi/generic3/mefenamic.htm): Mefenamic acid is
indicated for relief of mild to moderate pain in patients 14 years of age, when therapy will not exceed one week (7 days) and for treatment of primary dysmenorrhea. The recommended dose is 500
mg as an initial dose followed by 250 mg every 6 hours as needed, usually not to exceed one week.
Metabolism and elimination (http://www.rxlist.com/cgi/generic3/mefenamic.htm): Mefenamic acid is
metabolized by cytochrome P450 enzyme CYP2C9 to 3-hydroxymethyl mefenamic acid (Metabolite
I). Further oxidation to a 3-carboxymefenamic acid (Metabolite II) may occur. The activity of these
metabolites has not been studied. The metabolites may undergo glucuronidation and mefenamic acid
is also glucuronidated directly. Approximately 52 percent of a mefenamic acid dose is excreted into
the urine primarily as glucuronides of mefenamic acid (6%), 3-hydroxymefenamic acid (25%) and 3carboxymefenamic acid (21%). The proportion of free mefenamic acid in the urine is lower than 5 %
(compendium). The fecal route of elimination accounts for up to 20% of the dose, mainly in the form
of unconjugated 3-carboxymefenamic acid.
Medicines on sale in Switzerland: Méfé-basan, Ponstan®, Spiralgin®, etc.
Data on consumption: t (Switzerland)
Physical chemical properties:
Water solubility at pH 7.1 and 25°C
40 mg/L
Water solubility at pH 7.1 and 37°C
80 mg/L
Low solubility in chloroform and ether, slightly soluble in ethanol
Partition coefficient octanol/water (log Kow)
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Vapor pressure (20 °C)
Organic carbon-water partition coefficient (Koc)
Ocurrence in the environment:
To our knowledge, no study has been conducted to detect mefenamic acid in sewage treatment
plants or in the environment.
Ecotoxicity:
No data available
Toxicity:
Animal toxicity (Merck index)
LD50
Oral, mice
630 mg/kg
LD50
Oral, rat
790 mg/kg
Adverse effects on human (http://www.rxlist.com/cgi/generic3/mefenamic.htm)
The most frequently reported adverse experiences occurring in approximately 1-10% of patients are
abdominal pain, constipation, diarrhea, dyspepsia, flatulence, gross bleeding/perforation, heartburn,
nausea, GI ulcers (gastric/duodenal), vomiting, abnormal renal function, anemia, dizziness, edema,
elevated liver enzymes, headaches, increased bleeding time, pruritus, rashes, tinnitus.
Data on degradation:
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