Nonsteroidal anti-inflammatory drug and phospholipid prodrugs: Combination therapy with antisecretory agents in rats

Lichtenberger, Lenard M.; Ulloa, Carlos Manuel Ulloa; Romero, Jimmy J.; Vanous, Amy L.; Illich, Paul A.; Dial, Elizabeth J.

doi:10.1016/s0016-5085(96)70066-5

Cited by 49 publications

(37 citation statements)

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“…As amphiphilic surfactants, phospholipids could increase the solubility Brought to you by | MIT Libraries Authenticated Download Date | 5/13/18 3:36 AM of the drug by the action of wetting and dispersion (3,6). Unlike the non-polar nature of diclofenac, the complex showed amphiphilic nature, which may prove to be responsible for improved bioavailability of the drug (10).…”

Section: Resultsmentioning

confidence: 97%

Development and physicochemical evaluation of pharmacosomes of diclofenac

Semalty¹,

Semalty²,

Singh³

et al. 2009

Acta Pharmaceutica

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Diclofenac is one of the most widely prescribed non-steroidal anti-inflammatory drugs (NSAIDs). Use of diclofenac is associated with two major limitations; first, rare, but serious and sometimes fatal, gastrointestinal (GI) side-effects, including ulceration, and hemorrhage, especially in the elderly (1, 2), and second, poor water solubility. Pharmacosomes are amphiphilic lipid vesicular systems that have shown their potential in improving the bioavailability of poorly water soluble as well as poorly lipophilic drugs. Diclofenac is a poorly water soluble drug and also causes gastrointestinal toxicity. To improve the water solublity of diclofenac, its pharmacosomes (phospholipid complex) have been prepared and evaluated for physicochemical analysis. Diclofenac was complexed with phosphatidylcholine (80 %) in equimolar ratio, in the presence of dichloromethane, by the conventional solvent evaporation technique. Pharmacosomes thus prepared were evaluated for drug solubility, drug content, surface morphology (by scanning electron microscopy), phase transition behaviour (by differential scanning calorimetry), crystallinity (by X-ray powder diffraction) and in vitro dissolution. Pharmacosomes of diclofenac were found to be irregular or disc shaped with rough surfaces in SEM. Drug content was found to be 96.2 ± 1.1 %. DSC thermograms and XRPD data confirmed the formation of the phospholipid complex. Water solubility of the prepared complex was found to be 22.1 mg mL -1 as compared to 10.5 mg mL -1 of diclofenac. This improvement in water solubility in prepared pharmacosomes may result in improved dissolution and lower gastrointestinal toxicity. Pharmacosomes showed 87.8 % while the free diclofenac acid showed a total of only 60.4 % drug release at the end of 10 h of dissolution study.

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Section: Resultsmentioning

confidence: 97%

Development and physicochemical evaluation of pharmacosomes of diclofenac

Semalty¹,

Semalty²,

Singh³

et al. 2009

Acta Pharmaceutica

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“…Studies have shown that omeprazole has the ability to reduce the absorption and bioavailability of aspirin in animals 66 and by doing so has the ability to reduce the analgesic and antipyretic effects. 67 However, with respect to aspirin, the interaction is thought to lie in the PPIs' ability to increase intragastric pH and thereby reduce the absorption and thus bioavailability of aspirin, rather than inhibit the enzymes that metabolise it, as is the mechanism with clopidogrel. Aspirin is normally absorbed in a lipid-soluble state by diffusion.…”

Section: Further Controversy For Ppis?mentioning

confidence: 99%

Review article: proton pump inhibitors with clopidogrel - evidence for and against a clinically-important interaction

Disney

Watson

Blann

et al. 2011

Alimentary Pharmacology &Amp; Therapeutics

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Aliment Pharmacol Ther 2011; 33: 758–767 Summary Background The treatment of acute coronary syndromes involves a combination of antiplatelet therapies. Proton pump inhibitors are frequently recommended for patients receiving clopidogrel in addition to aspirin, to minimise the risk of bleeding. Several studies have shown that proton pump inhibitors can affect the platelet inhibitory effects of clopidogrel. However, the data on whether this has an effect on clinical outcomes are conflicting and a definitive answer is still awaited. Aim To provide an overview of the evidence for the pharmacological interaction between proton pump inhibitors and clopidogrel and to discuss whether this interaction translates into adverse clinical outcomes. Despite recent developments, clear consensus is lacking. Methods A search of the published literature combined with the authors’ knowledge of the field. Results There is evidence to show that proton pump inhibitors can influence the pharmacodynamics of clopidogrel, but the data suggesting clinical effects are weak and conflicting. Supporting a clinically important interaction are four retrospective studies including over 11 000 patients prescribed both clopidogrel and a proton pump inhibitor. Evidence against a clinically important interaction is derived from over 18 000 patients from seven studies, including the only prospective trial to examine the potential interaction. Confounding variables are relevant and prospective clinical evidence is lacking. Conclusions Proton pump inhibitors offer clear protection and the concern over clinically relevant interactions with clopidogrel is biologically plausible, but not yet proven.

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“…An increase in phospholipids makes the membrane more susceptible to peroxidation-induced damages. Numerous studies suggest that NSAIDs chemically associate with phospholipids and destabilize them from the mucous gel layer (Lichtenberger et al 1996), which would lead to increase in fluidity. In the present study increased phospholipid content in the intestinal BBM by NSAIDs is further supported by the fact that NSAIDs also increase the membrane fluidity as shown by Lucio et al (2004).…”

Section: Discussionmentioning

confidence: 99%

Alterations in the Lipid Profile and Membrane Dynamics of Rat Intestinal Brush Border Membrane Induced by Different Classes of Nonsteroidal Anti-Inflammatory Drugs

Sanyal

Sood

Kaushal

2007

Toxicology Mechanisms and Methods

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are known to cause gastrointestinal damage. New anti-inflammatory drugs have been developed in an attempt to improve their gastrointestinal side effect profile. Therefore, the objective of the present study was to compare the effect of three different NSAIDs, aspirin, nimesulide, and celecoxib, on the lipid profile and dynamics of rat intestinal brush border membranes (BBMs). Female Wistar rats were divided into four different groups viz: group I (control), group II (aspirin treated), group III (nimesulide treated), and group IV (celecoxib treated). Groups II, III, and IV received the corresponding drugs orally at a dose of 40 mg/kg body weight dissolved in water, while the control group received the vehicle only. After 28 days, all the treatment groups showed modification in the lipid profile of intestinal BBM as compared to control. Alterations in the intestinal membrane dynamics by fluidity studies showed a considerable increase, which correlated well with the changes in the lipid composition. It was suggested that NSAIDs such as aspirin, nimesulide, and celecoxib pose intestinal side effects due to initial changes in the composition and dynamics of the membranes. It was further concluded that newly discovered NSAIDs such as celecoxib have better safety profiles because of the less intense membrane effects, but studies are still required to comment decisively on the suitability of various NSAIDs depending upon their cyclooxygenase enzyme specificity.

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Nonsteroidal anti-inflammatory drug and phospholipid prodrugs: Combination therapy with antisecretory agents in rats

Cited by 49 publications

References 1 publication

Development and physicochemical evaluation of pharmacosomes of diclofenac

Development and physicochemical evaluation of pharmacosomes of diclofenac

Review article: proton pump inhibitors with clopidogrel - evidence for and against a clinically-important interaction

Alterations in the Lipid Profile and Membrane Dynamics of Rat Intestinal Brush Border Membrane Induced by Different Classes of Nonsteroidal Anti-Inflammatory Drugs

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