Pharmacological Properties of Diclofenac Sodium and Its Metabolites

Menassé, R.; Hedwall, P. R.; Kraetz, J.; Pericin, C.; Riesterer, L.; Sallmann, A; Ziel, R; Jaques, R.

doi:10.3109/03009747809097211

Cited by 193 publications

(89 citation statements)

References 20 publications

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“…Total body clearance remained unchanged Plasma diclofenac levels (ng/ml) for both groups of patients in spite of a 30% reduction in hepatic blood flow as reported previously (4,5). The present data showed wide interindividual variation for both groups when expressed as median: 3.50 CPB vs 5.03 ml min -1 kg -1 control, P = 0.13 (Table 1), or as range of variation IC95%: 2.91-4.43 ml min -1 kg -1 (CPB) and 3.32-6.03 ml min -1 kg -1 (control) (P>0.05).…”

Section: Introductionsupporting

confidence: 78%

“…During the postoperative period of cardiac surgery with cardiopulmonary bypass, there is a 30% reduction of hepatic blood flow accompanied by changes in the metabolism of diclofenac (4,5). The aim of the present study was to measure the pharmacokinetics and pharmacodynamics of diclofenac on the basis of plasma protein binding, during the postoperative period in surgical patients submitted or not to cardiopulmonary bypass.…”

Section: Introductionmentioning

confidence: 98%

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Diclofenac plasma protein binding: PK-PD modelling in cardiac patients submitted to cardiopulmonary bypass

Auler¹,

Espada²,

Crivelli³

et al. 1997

Braz J Med Biol Res

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Twenty-four surgical patients of both sexes without cardiac, hepatic, renal or endocrine dysfunctions were divided into two groups: 10 cardiac surgical patients submitted to myocardial revascularization and cardiopulmonary bypass (CPB), 3 females and 7 males aged 65 ± 11 years, 74 ± 16 kg body weight, 166 ± 9 cm height and 1.80 ± 0.21 m 2 body surface area (BSA), and control, 14 surgical patients not submitted to CPB, 11 female and 3 males aged 41 ± 14 years, 66 ± 14 kg body weight, 159 ± 9 cm height and 1.65 ± 0.16 m 2 BSA (mean ± SD). Sodium diclofenac (1 mg/kg, im Voltaren 75 ® twice a day) was administered to patients in the Recovery Unit 48 h after surgery. Venous blood samples were collected during a period of 0-12 h and analgesia was measured by the visual analogue scale (VAS) during the same period. Plasma diclofenac levels were measured by high performance liquid chromatography. A two-compartment open model was applied to obtain the plasma decay curve and to estimate kinetic parameters. Plasma diclofenac protein binding decreased whereas free plasma diclofenac levels were increased five-fold in CPB patients. Data obtained for analgesia reported as the maximum effect (E MAX ) were: 25% VAS (CPB) vs 10% VAS (control), P<0.05, median measured by the visual analogue scale where 100% is equivalent to the highest level of pain. To correlate the effect versus plasma diclofenac levels, the E MAX sigmoid model was applied. A prolongation of the mean residence time for maximum effect (MRTE MAX ) was observed without any change in lag-time in CPB in spite of the reduced analgesia reported for these patients, during the time-dose interval. In conclusion, the extent of plasma diclofenac protein binding was influenced by CPB with clinically relevant kinetic-dynamic consequences.

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Section: Introductionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 98%

Diclofenac plasma protein binding: PK-PD modelling in cardiac patients submitted to cardiopulmonary bypass

Auler¹,

Espada²,

Crivelli³

et al. 1997

Braz J Med Biol Res

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“…Diclofenac sodium is a non-steroidal anti-inflammatory drug (NSAID) that is widely prescribed and used for relieving the pain and edema associated with inflammatory conditions, such as osteoarthritis and rheumatoid arthritis [1][2][3] . It is commonly known that diclofenac acts by potent cyclo-oxygenase (COX) inhibition, which decreases the formation of proinflammatory mediators, such as prostaglandins (PGs) [4] .…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic-pharmacodynamic modeling of diclofenac in normal and Freund's complete adjuvant-induced arthritic rats

Zhang

Guo

et al. 2012

Acta Pharmacol Sin

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Aim: To characterize pharmacokinetic-pharmacodynamic modeling of diclofenac in Freund's complete adjuvant (FCA)-induced arthritic rats using prostaglandin E 2 (PGE 2 ) as a biomarker. Methods: The pharmacokinetics of diclofenac was investigated using 20-day-old arthritic rats. PGE 2 level in the rats was measured using an enzyme immunoassay. A pharmacokinetic-pharmacodynamic (PK-PD) model was developed to illustrate the relationship between the plasma concentration of diclofenac and the inhibition of PGE 2 production. The inhibition of diclofenac on lipopolysaccharide (LPS)-induced PGE 2 production in blood cells was investigated in vitro. Results: Similar pharmacokinetic behavior of diclofenac was found both in normal and FCA-induced arthritic rats. Diclofenac significantly decreased the plasma levels of PGE 2 in both normal and arthritic rats. The inhibitory effect on PGE 2 levels in the plasma was in proportion to the plasma concentration of diclofenac. No delay in the onset of inhibition was observed, suggesting that the effect compartment was located in the central compartment. An inhibitory effect sigmoid I max model was selected to characterize the relationship between the plasma concentration of diclofenac and the inhibition of PGE 2 production in vivo. The I max model was also used to illustrate the inhibition of diclofenac on LPS-induced PGE 2 production in blood cells in vitro. Conclusion: Arthritis induced by FCA does not alter the pharmacokinetic behaviors of diclofenac in rats, but the pharmacodynamics of diclofenac is slightly affected. A PK-PD model characterizing an inhibitory effect sigmoid I max can be used to fit the relationship between the plasma PGE 2 and diclofenac levels in both normal rats and FCA-induced arthritic rats.

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“…One would therefore expect more albumin-bound compounds to be present in the fluid of an inflamed joint than of a healthy joint. In humans, certain compounds (e.g., diclofenac) are known to accumulate at the site of inflammation, where they reach concentrations similar to those observed in plasma [211]. Although the maximum concentration of diclofenac in synovial fluid is lower than in plasma, its half-life is three times greater [212].…”

Section: Analysis Of Bone Bone Marrow and Synovial Fluidmentioning

confidence: 99%

Merging Wildlife and Environmental Monitoring Approaches with Forensic Principles: Application of Unconventional and Non-Invasive Sampling in Eco- Pharmacovigilance

Richards¹

2014

J Forensic Res

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Pharmaceutical residues in the environment have the potential to harm wildlife. A population's fragility or an animal's secretive nature may preclude capture and the use of invasive/destructive sampling techniques that are typically used in a risk assessment. Conventionally favoured matrices gathered opportunistically from carcasses have a finite lifespan, thereby limiting the detection window. This multidisciplinary paper aims to promote the use of non-invasive approaches and optimize use of even the most degraded carcasses. We highlight a selection of promising alternative, unconventional and underutilized sample types that could be applied in environmental monitoring efforts and wildlife forensic investigations. With a focus on non-steroidal anti-inflammatory drugs (NSAIDs), now under increasing scrutiny in the freshwater and terrestrial environment, we first illustrate current sampling practices and gaps in knowledge by summarizing exposure of: 1) aquatic organisms to urban effluent discharged into waterways, and, 2) scavenging species to veterinary residues in livestock and other carrion. We then consider the merits and limitations of a range of alternative environmentally robust sample options that offer a broader detection interval for NSAIDs, with emphasis on hair, wool and feathers. The viability of eyes/ocular material, bone matter, fecal matter, injection sites, ingesta/pellets and scavenging/coprophagous insects are also discussed.

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Pharmacological Properties of Diclofenac Sodium and Its Metabolites

Cited by 193 publications

References 20 publications

Diclofenac plasma protein binding: PK-PD modelling in cardiac patients submitted to cardiopulmonary bypass

Diclofenac plasma protein binding: PK-PD modelling in cardiac patients submitted to cardiopulmonary bypass

Pharmacokinetic-pharmacodynamic modeling of diclofenac in normal and Freund's complete adjuvant-induced arthritic rats

Merging Wildlife and Environmental Monitoring Approaches with Forensic Principles: Application of Unconventional and Non-Invasive Sampling in Eco- Pharmacovigilance

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