Sustained-release etodolac bioavailability and dose proportionality: correlation between in vivo and in vitro performance

Dey, Mike; Enever, R.P.; Marino, Mirko; Michelucci, J.; Smith, D.; Warner, Rochelle; Weierstall, R.

doi:10.1016/0378-5173(89)90110-5

Cited by 19 publications

(13 citation statements)

References 4 publications

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“…The time to achieve Cmax (tmax) of etodolac is most rapid when the drug is administered in solution, followed by solid regular-release formulations. As expected, tmax is longest when the drug is administered as a sustained release dosage form (Dey et al 1989). …”

Section: Absorptionmentioning

confidence: 89%

“…In calculating the total body clearance (CL), Dey et al (1989) assumed a value of 0.82 for bioavailability based on the recovery of radiolabelled drug in urine (Cayen et al 1981). However, when we reviewed the paper by Cayen et al (1981) we could find no such value for bioavailability.…”

Section: Absorptionmentioning

confidence: 97%

“…Both sustained release formulations yielded a significantly lower bioavailability than an aqueous solution. The bioavailability of a sustained release formulation of etodolac (UItradol® SR) is 78 to 84% of that of oral solutions (Dey et al 1989).…”

Section: Absorptionmentioning

confidence: 99%

“…The relative bioavailability of sustained release etodolac was studied by Dey et al (1989) in young male healthy volunteers. Two different sustained release formulations of etodolac were given; after 14 hours, 64 and 73% of the etodolac from these 2 formulations was released in an in vitro dissolution test.…”

Section: Absorptionmentioning

confidence: 99%

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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: 89%

Section: Absorptionmentioning

confidence: 97%

Section: Absorptionmentioning

confidence: 99%

Section: Absorptionmentioning

confidence: 99%

See 2 more Smart Citations

Etodolac Clinical Pharmacokinetics

Brocks

Jamali

1994

Clinical Pharmacokinetics

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“…A partir de então, surgiram diversos trabalhos com o objetivo de estabelecer correlação entre os parâmetros da dissolução in vitro e os parâmetros relativos aos estudos de biodisponibilidade in vivo (correlações in vitro-in vivo ou correlações iviv) (Aoyagi et al, 1982;Avico et al, 1976;Bramanti, 1973;Dey et al, 1989;Drewe, Guitard, 1993;Grdinic et al, 1979;Hayashi et al, 1995;Lin et al, 1990;Yau, Meyer, 1983).…”

Section: Introductionunclassified