3 DRUG PROFILE
3.1 ETODOLAC
Etodolac (ETD) belongs to a class of drug called non steroidal anti-inflammatory drug (NSADs). Other members of this class include aspirin, ibuprofen (Motrin, Advil, Nuprin, etc.), naproxen (Aleve, Naprosyn), indomethacin (Indocin), nabumetone (Relafen) and numerous others.
3.1.1 Physical Characteristics: - (Brittain et al, 2002), (Dollary, 1999).
IUPAC name : 1,8-Diethyl -1,3,4,9-tetrahydropyrano[3,4,-b] indole-1- acetic acid
Structure :
Molecular formula : C17H21NO3
Molecular weight : 287.354
Category : Non steroidal anti-inflammatory drugs (NSAIDs).
Description : White to off –white crystalline powder
Melting point : 145-148 °C
Taste : Characteristic
Solubility : ETD …show more content…
In-vitro studies have demonstrated greater inhibition of COX-2 than COX-1, in time independent and dependent assays as well as in assays utilizing heparinized whole blood from healthy volunteers (Woodfork and Dyke, 1997). In rats, it produces less suppression of gastric prostaglandins, PEG-2 and 6-Keto-PEG-1.
3.1.4 Pharmacodynamics
ETD is an anti-inflammatory agent with analgesic and antipyretic properties. It is used to treat osteoarthritis, rheumatoid arthritis and control acute pain. The therapeutic effects of ETD are achieved via inhibition of the synthesis of prostaglandins involved in fever, pain, swelling and inflammation. ETD is administered as a racemate. As with other NSAIDs, the S-form has been shown to be active while the R-form is inactive. Both enantiomers are stable and there is no evidence of R- to S- conversion in-vivo.
3.1.5 Pharmacokinetics …show more content…
The maximal plasma concentrations (Cmax) of ETD are achieved within 1-2 hours of administration of tablet or capsule.ETD is highly protein bound (greater than 95%). ETD distributes well into synovial fluid, the proposed primary site of action of NASID’ s. ETD is extensively metabolized, with almost no intact drug being recovered in urine. ETD does not undergo significant first-pass metabolism following oral administration. In human, ETD is metabolized mainly to 5 metabolites; acyl glucuronides; 6-hydroxyetodolac; 7-hydroxyetodolac; 8-(1’ –hyroxyethyl)-etodolac; 4-ureido-etodolac. The metabolites further form glucuronide conjugates (Brittain et al, 2002).
Distribution
The mean apparent volume of distribution (Vd/F) of ETD is approximately 390 ml/kg. ETD is more than 99% bound to plasma proteins, primarily to albumin. The free fraction is less than 1% and is independent of ETD total concentration over the dose range studied. It is not known whether ETD is excreted in human milk; however, based on its physical-chemical properties, excretion into breast milk is expected.
3.1 ETODOLAC
Etodolac (ETD) belongs to a class of drug called non steroidal anti-inflammatory drug (NSADs). Other members of this class include aspirin, ibuprofen (Motrin, Advil, Nuprin, etc.), naproxen (Aleve, Naprosyn), indomethacin (Indocin), nabumetone (Relafen) and numerous others.
3.1.1 Physical Characteristics: - (Brittain et al, 2002), (Dollary, 1999).
IUPAC name : 1,8-Diethyl -1,3,4,9-tetrahydropyrano[3,4,-b] indole-1- acetic acid
Structure :
Molecular formula : C17H21NO3
Molecular weight : 287.354
Category : Non steroidal anti-inflammatory drugs (NSAIDs).
Description : White to off –white crystalline powder
Melting point : 145-148 °C
Taste : Characteristic
Solubility : ETD …show more content…
In-vitro studies have demonstrated greater inhibition of COX-2 than COX-1, in time independent and dependent assays as well as in assays utilizing heparinized whole blood from healthy volunteers (Woodfork and Dyke, 1997). In rats, it produces less suppression of gastric prostaglandins, PEG-2 and 6-Keto-PEG-1.
3.1.4 Pharmacodynamics
ETD is an anti-inflammatory agent with analgesic and antipyretic properties. It is used to treat osteoarthritis, rheumatoid arthritis and control acute pain. The therapeutic effects of ETD are achieved via inhibition of the synthesis of prostaglandins involved in fever, pain, swelling and inflammation. ETD is administered as a racemate. As with other NSAIDs, the S-form has been shown to be active while the R-form is inactive. Both enantiomers are stable and there is no evidence of R- to S- conversion in-vivo.
3.1.5 Pharmacokinetics …show more content…
The maximal plasma concentrations (Cmax) of ETD are achieved within 1-2 hours of administration of tablet or capsule.ETD is highly protein bound (greater than 95%). ETD distributes well into synovial fluid, the proposed primary site of action of NASID’ s. ETD is extensively metabolized, with almost no intact drug being recovered in urine. ETD does not undergo significant first-pass metabolism following oral administration. In human, ETD is metabolized mainly to 5 metabolites; acyl glucuronides; 6-hydroxyetodolac; 7-hydroxyetodolac; 8-(1’ –hyroxyethyl)-etodolac; 4-ureido-etodolac. The metabolites further form glucuronide conjugates (Brittain et al, 2002).
Distribution
The mean apparent volume of distribution (Vd/F) of ETD is approximately 390 ml/kg. ETD is more than 99% bound to plasma proteins, primarily to albumin. The free fraction is less than 1% and is independent of ETD total concentration over the dose range studied. It is not known whether ETD is excreted in human milk; however, based on its physical-chemical properties, excretion into breast milk is expected.