Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Etodolac is a chiral nonsteroidal anti-inflammatory drug (NSAID) that is marked as the racemate. Currently, the drug is available in several countries for the treatment of arthritis and the alleviation of pain. Etodolac possesses several unique disposition features mainly due to its stereoselective pharmacokinetics. In plasma, the concentrations of the 'inactive' R-enantiomer are about 10-fold higher than those of the active S-enantiomer, an observation that is novel among the chiral NSAIDs. In common with other NSAIDs, the drug is highly plasma protein bound, and undergoes virtually complete biotransformation to oxidised metabolites and acyl-glucuronides. Etodolac is well absorbed, with maximal plasma concentrations attained within 1 to 2 hours in healthy volunteers. The area under the plasma concentration-time curve of racemic etodolac increases linearly with doses used clinically. The elimination half-life of etodolac is between 6 and 8 hours in plasma, and is similar for both enantiomers. The volume of distribution (Vd) of racemic etodolac is higher than that of most other NSAIDs mainly because of the extensive distribution of the S-enantiomer. The very large Vd of the S-enantiomer, compared with its antipode is, at least in part, due to its less extensive plasma protein binding. In addition to the unchanged drug, substantial concentrations of the acyl-glucuronides of etodolac are found in both plasma and the synovial fluid of patients with arthritis. A limited amount of conjugated etodolac is found in the bile of patients following cholecystectomy. Hepatic cirrhosis has no effect on the pharmacokinetics of racemic etodolac, although the effect of hepatic dysfunction on the pharmacokinetics of the individual enantiomers has yet to be determined. In elderly non-arthritic individuals with excellent kidney function, aging does not affect the pharmacokinetics of etodolac. The pharmacokinetics of the drug in patients with renal failure have not been published, and may be important because the acyl-glucuronides are renally cleared.
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PMID:Etodolac clinical pharmacokinetics. 801 60

Etodolac exhibits linear pharmacokinetics, good oral bioavailability, greater than 99% protein binding, a low oral clearance (almost exclusively non-renal), a relatively small volume of distribution and a half-life that averages 7.3 +/- 4.0 h. No significant pharmacokinetic differences have been noted in patients with mild to moderate renal impairment, in patients with cirrhosis, in the elderly or in patients with arthritis. The pharmacodynamics of the drug are well characterized in terms of pain intensity differences (PID) yielding an EC50 of 13 micrograms/ml. The extensive kinetic/dynamic characterization of etodolac, together with its short half-life, makes the drug an ideal candidate for a sustained-release (SR), once-a-day formulation. Etodolac SR formulations exhibit the same pharmacokinetic characteristics as the conventional-release (CR) formulation, except for a longer time to peak concentration and a lower peak concentration. Fluctuation ratios upon multiple dosing are comparable for equal total daily doses of etodolac SR and twice-daily doses of the CR formulation. Administration with food (high-fat meal) did not affect areas under the curve for either the CR or the SR product. Simulation analyses for etodolac SR suggest that PID responses are maintained over 24 h.
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PMID:Pharmacokinetics of sustained-release etodolac. 821 Sep 22