Differentiating among nonsteroidal antiinflammatory drugsby pharmacokinetic and pharmacodynamic profiles

Fenner, Helmut

doi:10.1016/s0049-0172(97)80050-9

Cited by 30 publications

(17 citation statements)

References 9 publications

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“…Furthermore, in terms of clinically effective analgesic activity, full PGE 2 inhibition is not required. If plasma ibuprofen concentration reaches the minimum level required to inhibit COX2 to achieve a clinical effect, pain relief is possible in the early phase following drug administration, regardless of the T max or I max 22,23…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen

Shin¹,

Lee²,

Ha³

et al. 2017

DDDT

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ObjectiveProstaglandin E2 (PGE2) synthesis is modulated by COX2. Changes in PGE2 could be used to quantify the COX2 inhibition after ibuprofen administration. This study investigated the pharmacokinetic and pharmacodynamic relationships for COX2 inhibition according to three formulations of ibuprofen in healthy male subjects.Materials and methodsA randomized, open-label, single-dose, three-treatment, six-sequence crossover study was performed in 36 healthy South Korean male volunteers. Enrolled subjects received the following three 200 mg ibuprofen formulations: ibuprofen arginine, solubilized ibuprofen capsule, and standard ibuprofen. Pharmacokinetic and pharmacodynamic blood samples were collected for 16 hours following treatment. For pharmacodynamic evaluations, lipopolysaccharide (LPS)-induced PGE2 inhibition at each time point compared to predose was measured. Noncompartmental analysis was used for pharmacokinetic assessment, and time-weighted average inhibition (WAI) of PGE2 was applied to the pharmacodynamic evaluation.ResultsAfter a single oral dose of the ibuprofen formulations, the median times to maximum concentration were 0.42, 0.5, and 1.25 hours in ibuprofen arginine, solubilized ibuprofen capsule, and ibuprofen, respectively. The maximum observed plasma concentration was lower in ibuprofen, and the area under the plasma concentration–time curve was comparable among the three formulations. A significant difference was observed between fast-acting formulations and standard ibuprofen tablets for both maximum concentration and time taken to reach it. Individual formulations had an effect on PGE2 WAI during the 8 hours following treatment, resulting in significantly lower WAI in standard ibuprofen: ibuprofen arginine 18.4%, solubilized ibuprofen capsule 18.4%, and standard ibuprofen 11.6%.ConclusionRapid absorption and higher peak concentration were observed in ibuprofen arginine and the solubilized ibuprofen capsule. Additionally, fast-acting formulations had more predominant inhibitory activity on the COX2 enzyme.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen

Shin¹,

Lee²,

Ha³

et al. 2017

DDDT

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“…If plasma ibuprofen concentration reaches the minimum level required to inhibit COX2 to achieve a clinical effect, pain relief is possible in the early phase following drug administration, regardless of the T max or I max . 22,23 Although these results clearly describe the pharmacokineticpharmacodynamic relationship of ibuprofen according to different formulations, there were some limitations in this clinical study. Because this study was a single study with a relatively low dose, considering the sigmoidal concentrationeffect curves, complete or full-range COX2 inhibition was not routinely observed.…”

mentioning

confidence: 88%

Pharmacokinetic and Pharmacodynamic Evaluation According to the Absorption Differences in Three Formulations of Ibuprofen

Kim

Choi

Park

et al. 2017

Clinical Therapeutics

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“…Indeed it could be that kinetic conditions at high concentration-response curves (i.e., at 80% inhibition values) where there is non-linearity and high error could lead to aberrations in the results. Also, peak-trough plasma concentrations are probably more valid for making comparisons with in vitro data [60]. There may be just as valid comparisons at the low end of the plasma concentrations where there may be different kinetic responses with NSAIDs.…”

Section: Cox-2 Selectivitymentioning

confidence: 99%

“…The relationship of plasma concentrations of NSAIDs to their expected COX-1 and COX-2 inhibition based on in vitro data has been explored for both relevance to the clinical outcomes (pain, anti-inflammatory activities) as well as in vivo situations [60,61]. In a comparison of pharmacokinetics of nimesulide after its administration by various routes to dogs with effects on COX isoforms in vitro using the whole blood assay, Toutain et al [31] observed that the IC 50 for inhibition of COX-2 and COX-1 was 1.6 and 20.3 mmol/L, respectively.…”

Section: Cox-2 Selectivitymentioning

confidence: 99%

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Pharmacological properties of nimesulide

Rainsford

Bevilacqua

Dallegri³

et al. 2005

Nimesulide — Actions and Uses

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Arthritis [11] granuloma [11] Exudate Volume Leucocytes in Rats [11] DRUG ED 40 (CI) mg/kg/d ED 30 (CI) mg/kg ED 30 mg/kg ED 50 (Cl) mg/kgNimesulide 1.6 (0.07-38) 0.65 (0.18-2.3)~1.0~1.5 11 (3.9-28) Ibuprofen 75 (11-500) 45 (10-198) N/D N/D 16 (6.1-40) Indomethacin 0.8 (0.03-23) 1.2 (0.31-5.9)~0.3~0.2 1.1 (0.4-3.0) Ratio-Nimesulide/ 2.0 0.54 0.3 7.5 10.0 Indomethacin Nimesulide/ 0.021 0.014 N/D N/D 0.69 Ibuprofen CI = 95% confidence interval. N/D = not determined. 140 K. D. Rainsford et al.∑ Arachidonic acid metabolism, especially production of COX-2 derived prostaglandins and leukotrienes ∑ Proinflammatory cytokine production and actions, especially of tumour necrosis factor-a (TNFa) and interleukins (IL), 1, 6 and 8

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Differentiating among nonsteroidal antiinflammatory drugsby pharmacokinetic and pharmacodynamic profiles

Cited by 30 publications

References 9 publications

Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen

Pharmacokinetic and pharmacodynamic evaluation according to absorption differences in three formulations of ibuprofen

Pharmacokinetic and Pharmacodynamic Evaluation According to the Absorption Differences in Three Formulations of Ibuprofen

Pharmacological properties of nimesulide

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