Bioavailability and Bioequivalence of Two Formulations of Etodolac (Tablets and Suppositories)

Molina‐Martínez, Irene T.; Herrero, Rocío Carande; Gutiérrez, Julián; Iglesias, J M Reguera; Fábregas, Jaime; Martinez-Tobed, A.; Cadórniga, R

doi:10.1002/jps.2600820220

Cited by 8 publications

(8 citation statements)

References 5 publications

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“…This concern may become even more consequential when there exists a marginal difference in total plasma concentrations between the products. Indeed the insignificant differences between suppositories and tablets observed by Molina-Martinez et al (1993) [table II] might have been significant if the plasma concentration of the S-etodolac had been measured.…”

Section: Absorptionmentioning

confidence: 92%

“…Furthermore, despite the availability of alternative assays, there are still reports appearing in the literature based on similar methods (e.g. Molina-Martinez et al 1993). described a gas chromatographic method that involved a precolumn derivatisation of etodolac with S-( + )-amphetamine.…”

Section: Methodsmentioning

confidence: 97%

“…Spontaneous hydrolysis of these metabolites results in the release of parent etodolac if proper analytical procedures are not followed. Unfortunately, the assay described by Cosyns et al (1983) and used by Molina-Martinez et al (1993) in the study described above did not seem to involve precautions to prevent the spontaneous hydrolysis of the conjugated etodolac.…”

Section: Absorptionmentioning

confidence: 93%

“…Very recently, bioequivalence of an etodolac suppository has been assessed against a tablet formulation (Molina-Martinez et al 1993). Despite a 30% lower Cmax and somewhat slower absorption rate, the authors suggested that the suppository was bioequivalent to the tablet because area under the plasma concentration-time curve (AUC) and tmax values of the products were within 100 ± 20% of one another.…”

Section: Absorptionmentioning

confidence: 98%

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Etodolac Clinical Pharmacokinetics

Brocks

Jamali

1994

Clinical Pharmacokinetics

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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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Section: Absorptionmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 97%

Section: Absorptionmentioning

confidence: 93%

Section: Absorptionmentioning

confidence: 98%

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Etodolac Clinical Pharmacokinetics

Brocks

Jamali

1994

Clinical Pharmacokinetics

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“…Human biological fluids were analysed by capillary GC and separated metabolites were identified by MS in a full screen mode [50,51]. Different LC procedures for separation and determination of ETD in plasma using UV detection were reported [52][53][54]. HPTLC determination of ETD in formulations and human plasma has been described [55].…”

Section: Chromatographic Methodsmentioning

confidence: 99%