Pharmacological aspects of chiral nonsteroidal anti‐inflammatory drugs

Muller, Noëlle; Payan, E.; Lapicque, Françoise; Bannwarth, B; Netter, Patrick

doi:10.1111/j.1472-8206.1990.tb00042.x

Cited by 38 publications

(13 citation statements)

References 61 publications

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“…The R( -) enantiomer can, however, have analgesic effects, as demonstrated with flurbiprofen (Brune et al 1991). The pharmacokinetic characteristics of the enantiomers usually observed after administration of a racemic mixture differ for some of these drugs (ibuprofen, etodolac, flurbiprofen), while both enantiomers of other compounds present an identical behaviour (ketoprofen) [Jamali 1988;Muller et al 1990]. Furthermore, in some species, the R form of several NSAIDs could undergo unidirectional metabolic inversion to its S mirror-image, by action of a stereospecific enzyme, acety1coenzyme Athioesterase.…”

mentioning

confidence: 96%

Protein Binding and Stereoselectivity of Nonsteroidal Anti-Inflammatory Drugs

Lapicque¹,

Muller²,

Payan³

et al. 1993

Clinical Pharmacokinetics

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Stereoselective binding of nonsteroidal anti-inflammatory drugs (NSAIDs) can be studied using various techniques. Thus the results obtained by different investigators may be poorly consistent and even contradictory. NSAIDs are bound stereoselectively to serum albumin to different degrees depending on the drug investigated (ibuprofen, indoprofen, carprofen, etodolac, ketoprofen and flurbiprofen). For other drugs, both enantiomers are bound to a similar extent (pirprofen, fenoprofen). This stereoselectivity could vary with experimental conditions, in particular with protein concentration (ketoprofen, etodolac), leading to individual differences. Finally, the stereoselectivity of protein binding and of pharmacokinetics can be compared: differences in binding between enantiomers can explain their differences in pharmacokinetics, once metabolic properties such as inversion have been taken into account.

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mentioning

confidence: 96%

Protein Binding and Stereoselectivity of Nonsteroidal Anti-Inflammatory Drugs

Lapicque¹,

Muller²,

Payan³

et al. 1993

Clinical Pharmacokinetics

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“…Physiologic characteristics such as metabolic profile (Knihinicki et al, 1990;Rudy et al, 1991), protein binding in serum (Lagrange et al, 2000;Nagao et al, 2003), plasma concentrations (Foster and Jamali, 1988;Geisslinger et al, 1993Geisslinger et al, , 1994Patel et al, 2003), as well as pharmacologic effects (Muller et al, 1990), differ among enantiomers. Accordingly, the effect of NSAIDs and NSAIDs-Glu on the renal excretion of MTX probably differs among enantiomers or diastereomers.…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Inhibition of Methotrexate Excretion by Glucuronides of Nonsteroidal Anti-inflammatory Drugs via Multidrug Resistance Proteins 2 and 4

Kawase

Yamamoto

Egashira

et al. 2015

Journal of Pharmacology and Experimental Therapeutics

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Combined administration of methotrexate (MTX) and nonsteroidal anti-inflammatory drugs (NSAIDs) can result in a decreased systemic clearance of MTX. To date, inhibition of renal uptake via organic anion transporters and efflux via multidrug resistance-associated protein (MRPs) by NSAIDs has been recognized as possible sites of drug interaction between MTX and NSAIDs. Although most NSAIDs are glucuronidated in kidney tissue and excreted mainly as glucuronide conjugates, it is not fully known whether the glucuronides of NSAIDs (NSAIDs-Glu) inhibit MTX excretion via MRP2 and MRP4. The purpose of this study was to investigate the inhibitory effects of the glucuronides of several NSAIDs (diclofenac, R-and S-ibuprofen, R-and S-flurbiprofen, and R-and S-naproxen), as well as the parent NSAIDs on MTX uptake using human MRP2-and MRP4-expressing inside-out vesicles. Results confirm that all NSAIDs and NSAIDs-Glu examined exhibited stereoselective and concentrationdependent inhibitory effects on MTX uptake via MRP2 and MRP4. Notably, NSAIDs-Glu potently inhibited MTX uptake via MRP2 and MRP4 compared with the corresponding parent NSAIDs except for naproxen in MRP2 and S-flurbiprofen in MRP4. The present results support that the glucuronides of NSAIDs, as well as the parent NSAIDs, are involved in the inhibition of urinary excretion of MTX via MRP2 and MRP4.

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“…The NSAIDs are classified into different groups based on their chemical structure and mechanism of action (Table 1). NSAIDs are generally chiral molecules (except diclofenac), but mostly a single enantiomer is pharmacologically active [26]. …”

Section: Properties Of Nsaidsmentioning

confidence: 99%

Current Perspectives in NSAID-Induced Gastropathy

Sinha

Gautam

Shukla

et al. 2013

Mediators of Inflammation

105

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, anti-inflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection.

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Pharmacological aspects of chiral nonsteroidal anti‐inflammatory drugs

Cited by 38 publications

References 61 publications

Protein Binding and Stereoselectivity of Nonsteroidal Anti-Inflammatory Drugs

Protein Binding and Stereoselectivity of Nonsteroidal Anti-Inflammatory Drugs

Stereoselective Inhibition of Methotrexate Excretion by Glucuronides of Nonsteroidal Anti-inflammatory Drugs via Multidrug Resistance Proteins 2 and 4

Current Perspectives in NSAID-Induced Gastropathy

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