Pharmacokinetics of tiaprofenic acid in normal rabbits and rabbits subjected to joint immobilisation

Meyer-Carrive, Isabelle; Graham, Garry G.; Ghosh, Peter

doi:10.1007/bf01975715

Cited by 5 publications

(4 citation statements)

References 19 publications

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“…For example, radioactivity in the carageenan-inflamed paws was higher in comparison to the non-inflamed paws, regardless of the type of NSAIDs (7). Similar results were observed in the rabbit model of joint immobilisation, using a non-immobilised contralateral joint as control, after subcutaneous administration of tiaprofenic acid, another member of the propionic acid family (8).…”

Section: Discussionsupporting

confidence: 68%

Pharmacokinetics of ketoprofen in rabbit after a single topical application

Audeval-Gerard

Nivet

Amrani

et al. 2000

Eur. J. Drug Metab. Pharacokinet.

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used by topical application in management of joint pain and inflammation. Little is known, however, about their pharmacokinetics, especially in the synovial compartment versus the plasma compartment, following topical administration. Ketoprofen, a NSAID, was delivered by a single topical application (KETUM 2.5% gel) on the rabbit knee-joint region of one hind limb. Concentrations of ketoprofen were measured in plasma, synovial fluid, joint capsule and synovial fat tissue at 2, 4, 6 and 12 hours after application. Whatever the time period after application, ketoprofen concentrations in synovial fluid were much higher than in plasma. The time-course of the decrease in ketoprofen plasma concentrations was more rapid than that in synovial fluid. Similarly, concentrations in joint capsule were higher than those found in synovial fat tissue. Finally, while ketoprofen concentrations decreased rapidly in plasma and in synovial fat tissue, concentrations in joint capsule and particularly in synovial fluid were more sustained. The increase in residence time of ketoprofen in synovial fluid could be in favour of its efficiency in the management of joint pain and inflammation.

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Section: Discussionsupporting

confidence: 68%

Pharmacokinetics of ketoprofen in rabbit after a single topical application

Audeval-Gerard

Nivet

Amrani

et al. 2000

Eur. J. Drug Metab. Pharacokinet.

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“…The reason for these similar values lies in the factors controlling the AUC values. From the compartmental model, it can be shown that the ratio of the AUC values is controlled by the ratio of clearances into and out of synovial fluid [14,15]. A similar relationship exists for the ratio AUCb/AUC.…”

Section: Pharmacokinetics Of Enantiomers In Blood Blister and Synovimentioning

confidence: 82%

“…These were k Vc/ks V and kspbV Ikbp Vb. These ratios represent the ratios of the clearances of the drugs into and out of synovial and blister fluids, respectively [14,15]. The areas under the time-course of drug concentrations in plasma, synovial and blister fluids (AUC, AUCS and AUCb) were determined by trapezoidal integration.…”

Section: Pharmacokinetic Modellingmentioning

confidence: 99%

The stereoselective disposition of the enantiomers of ibuprofen in blood, blister and synovial fluid.

Seideman

Lohrer

Graham

et al. 1994

Brit J Clinical Pharma

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1 A sensitive, stereospecific assay using gas chromatography-mass spectrometry (GC/MS) was established to measure the concentrations of the enantiomers of ibuprofen in small volumes (50 gl) of blister fluid.2 The concentrations of the enantiomers in blister fluid, assessed in eight patients, were similar to those in synovial fluid, both fluids behaving as peripheral compartments with respect to plasma.3 The mean rate constants of transfer of R-ibuprofen into (0.14 ± 0.06 h-1) and out of (0.20 ± 0.04 h-1) blister fluid were not significantly different from those for synovial fluid (0.19 ± 0.12 h-1, 0.34 ± 0.11 h-1, respectively). Similarly, the mean rate constants of transfer of S-ibuprofen into (0.22 ± 0.07 h-1) and out of (0.27 + 0.08 h-1) blister fluid were not significantly different from those for synovial fluid (0.29 ± 0.10, 0.36 ± 0.11 h-1). However, the correlations were poor between the transfer constants for each of the enantiomers between plasma, and both blister and synovial fluid (P > 0.2). 4 The complex rate constant of transfer of S-ibuprofen into blister fluid (0.22 + 0.07 h-1) was greater than that of R-ibuprofen (0.14 ± 0.07 h-1), which may be explained by the lesser protein binding of the S-enantiomer. 5 The mean AUC of the S-enantiomer was greater than of the R-enantiomer in both blister (116 ± 43 mg 1-' h, 73 ± 32 mg 1-l h, respectively; P < 0.05) and in synovial fluid (110 ± 28 mg 1-' h, 56 ± 8 mg 1-F h, respectively; P < 0.01). The difference between the mean AUC values of the enantiomers in synovial fluid vs blister fluid was not significant. 6 Despite similar concentration-time profiles, and mean pharmacokinetic parameters, blister fluid was not a good model for predicting the kinetics of the enantiomers of ibuprofen in synovial fluid in individual patients. However, the blister as a peripheral compartment, better simulates the time course of concentrations in synovial fluid than does plasma, and consequently drug concentrations therein might better relate to clinical efficacy than do those in plasma.

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“…Animals were sacrificed after the last drug application, and 24 h urine were collected at this time point, and stored at ¹80 8 C. Urinary creatinine was measured using a commercially available test kit (Sigma Deisenhofen, Germany), based on the established picrinic acid method [17]. Drug levels in plasma were determined similarly to [16]. 30 and 120 min after the last application of 5 mg/kg tiaprofenic acid the drug levels were 18 and 10 g/ml.…”

Section: Animalsmentioning

confidence: 99%

Effects of tiaprofenic acid on urinary pyridinium crosslinks in adjuvant arthritic rats: Comparison with doxycycline

et al. 1997

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In arthritic rats tiaprofenic acid has not only the capability to suppress paw inflammation, but also to prevent with high potency the excretion of pyridinium crosslinks. Doxycycline without inherent antiinflammatory activity does not exhibit such preserving effects on collagen degradation in this model. Thus the mode of action of cartilage protecting drugs within the complex pathogenesis of arthritis will need further elucidation.

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Pharmacokinetics of tiaprofenic acid in normal rabbits and rabbits subjected to joint immobilisation

Cited by 5 publications

References 19 publications

Pharmacokinetics of ketoprofen in rabbit after a single topical application

Pharmacokinetics of ketoprofen in rabbit after a single topical application

The stereoselective disposition of the enantiomers of ibuprofen in blood, blister and synovial fluid.

Effects of tiaprofenic acid on urinary pyridinium crosslinks in adjuvant arthritic rats: Comparison with doxycycline

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