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Medical research on naproxen
The effect of naproxen sodium on experimental otitis media.
Kulak Burun Bogaz Ihtis Derg. 2008 Jan-Feb; 18(1): 14-18
Kayhan FT, Algün Z
OBJECTIVES: We evaluated the effect of naproxen sodium on propylene glycol-induced otitis media in guinea pig ears. MATERIALS AND METHODS: Twenty adult guinea pigs were randomized to the study and control groups equal in number. A single dose of propylene glycol (0.2 ml, 60%) was applied to the left ears of the control group and to both ears of the study group. Saline solution was applied to the right ears of the control group. After propylene glycol application, the study group received naproxen sodium (oral, 10 mg/kg daily) for 15 days, whereas the control ears were left untreated. At the end of four weeks, the animals were decapitated under anesthesia. Otoscopic examination was performed and temporal bones were removed for histologic examination under light microscopy. RESULTS: Nine animals were alive in each group at the end of four weeks. In the control group, all the right ears receiving saline solution were normal, whereas otitis media and inflammatory changes were observed in six of the left ears receiving propylene glycol. In the study animals treated with naproxen sodium, otitis media and tympanic membrane perforation were seen in 14 ears. Of these, three ears had purulent, 11 ears had serous effusion. Epithelial hyperplasia (n=10), keratinizing epithelium and cholesteatoma formation (n=4) were also observed. CONCLUSION: Our results suggest that the administered dose of systemic naproxen sodium has no inhibitory effect on the development of inflammation and otitis media.
Nonaspirin NSAIDs, Cyclooxygenase 2 Inhibitors, and the Risk for Stroke.
Stroke. 2008 Apr 24;
Roumie CL, Mitchel EF, Kaltenbach L, Arbogast PG, Gideon P, Griffin MR
BACKGROUND AND PURPOSE: There is limited information regarding the cerebrovascular safety of cyclooxygenase 2 inhibitors (coxibs) and noncoxib nonsteroidal antiinflammatory drugs (NSAIDs). We determined whether specific NSAIDs, including coxibs, are associated with risk of stroke. METHODS: Retrospective cohort study among Tennessee Medicaid enrollees aged 50 to 84 years between January 1, 1999 and December 31, 2004. Noninstitutionalized persons with continuous enrollment in Medicaid and no stroke or other serious medical illness in the year before cohort entry were included. The 7 most common NSAIDs were examined: celecoxib, rofecoxib, valdecoxib, ibuprofen, naproxen, diclofenac, and indomethacin. Nonuse of NSAIDs was the reference group. Because new use is less susceptible to bias, we conducted a similar analysis confined to new users. The outcome was hospitalization for an incident cerebrovascular event: ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. RESULTS: The cohort included 336 906 persons, with 989 826 person-years of follow-up, and 4354 stroke hospitalizations. There were 4.51 strokes per 1000 person years in the nonuse group, 5.15 strokes per 1000 person years (adjusted HR 1.28, 95% CI 1.06, 1.53) with rofecoxib use, and 5.95 strokes per 1000 person years (adjusted HR 1.41, 95% CI 1.04, 1.91) with valdecoxib use. New use of rofecoxib and valdecoxib led to 6.06 (adjusted HR 1.46 95% CI 1.08, 1.98) and 6.19 (adjusted HR 1.39, 95% CI 0.74, 2.59) strokes per 1000 person years respectively. No other NSAID significantly increased the risk of incident stroke. CONCLUSIONS: Our results indicate an increased risk of stroke with current use of two highly selective coxibs, rofecoxib and valdecoxib, also shown to increase cardiovascular risk. These results also provide some reassurance about other specific NSAIDs regarding stroke risk.
Environ Toxicol Chem. 2008 Apr 17; 1
Topp E, Hendel J, Lapen D, Chapman R
Naproxen (2-(6-methoxy-2-naphthyl) propionic acid) is widely used for the treatment of pain and swelling associated with arthritis, gout and other inflammatory conditions. Naproxen has been detected in municipal sewage outflows, and in surface waters, and could reach agricultural land through the application of municipal biosolids or reclaimed water. The persistence characteristics of naproxen in three agricultural soils were investigated. In laboratory microcosms of moist soil incubated at 30oC, [O-CH3-14C]-naproxen was rapidly and thoroughly mineralized to 14CO2 with comparable kinetics in a sandy loam, a loam soil, and a silt loam soil. Naproxen mineralization was responsive to soil temperature and soil moisture content, consistent with the primary mechanism of dissipation being biodegradation. Mineralization of naproxen was hastened by the addition of liquid municipal biosolids (LMB) from a municipal sewage-treatment plant that aerated this material. Naproxen was stable in autoclaved soils with or without addition of autoclaved LMB, whereas naproxen was rapidly mineralized in sterile soil supplemented with non-sterile LMB. An enrichment culture was obtained from aerobically-digested LMB in a mineral salts medium with naproxen as the sole source of carbon. The culture converted the parent compound to the corresponding naphthol, O-desmethyl-naproxen. In summary, naproxen was rapidly removed from soil with mesophilic aerobic biodegradation being the primary mechanism of dissipation. Microorganisms carried in biosolids enhanced naproxen dissipation in soil, with the initial mechanism of attack likely O-demethylation. We conclude on this basis that naproxen in soils receiving biosolids would be readily biodegradable, and consequently pose little risk of contamination of adjacent water or crops.
Sci Total Environ. 2008 Apr 11;
Peng X, Yu Y, Tang C, Tan J, Huang Q, Wang Z
A scoping study was conducted to investigate the residues of nineteen pharmaceuticals and personal care products (PPCPs), including 4 natural and 3 synthetic steroid estrogens, 7 endocrine-disrupting phenols, and 5 acid pharmaceuticals in three urban streams and the Major Pearl River at Guangzhou, a megapolis in the Pearl River Delta, South China. Estrone was detected in >60% water samples with a maximum concentration of 65 ng L(-1). Endocrine-disrupting phenols (nonylphenol, bisphenol A, triclosan, 2-phenylphenol, methyparaben, and propylparaben) were found to be widely present at rather high concentrations in the urban riverine water of Guangzhou. Salicylic acid, clofibric acid and ibuprofen were detected in most water samples with maximum concentrations of 2098, 248 and 1417 ng L(-1) respectively, whereas naproxen was less frequently detected and also at lower concentration. Both the detection frequencies and median concentrations of the PPCPs appeared higher during the low-flow season than during the high-flow season. The seasonal difference in PPCPs occurrence was probably attributed to the dilution effect caused by the rainfall. PPCPs in the urban riverine water of Guangzhou originated mainly from random discharge and/or leakage of municipal wastewater. PPCPs contamination in the Major Pearl River may be of a potential environmental issue, especially during the low-flow season.
Toxicol In Vitro. 2008 Mar 4;
Thibaut R, Porte C
Effects of 11 pharmaceuticals belonging to three therapeutic classes (lipid regulators from the fibrate group, non-steroidal anti-inflammatory drugs and anti-depressives from the selective serotonin reuptake inhibitors group) were assessed in the fish hepatoma cell line (PLHC-1) by looking at cytotoxicity and interactions with cytochrome P450 1A (CYP1A) function. Among the tested pharmaceuticals, fluoxetine and paroxetine exerted cytotoxic effects, cell viability decreased to 52% and 6% after 24h of exposure to 20muM fluoxetine and paroxetine, respectively. The cytotoxicity of both compounds was modulated by cytochrome P450 inhibitors and was dramatically reduced when culture medium was supplemented with reduced glutathione and vitamin E succinate. Additionally, exposure of PLHC-1 cells to some pharmaceuticals led to an early and transient induction of ethoxyresorufin O-deethylase (EROD) activity: bezafibrate and antidepressants induced EROD activity at a concentration of 1muM whereas clofibrate, ibuprofen and naproxen acted as inducers at a higher concentration (10muM). These effects might be of toxicological concern since alterations of CYP1A may affect xenobiotic metabolism and toxicity.
Free drug metabolic clearance in elderly people.
Clin Pharmacokinet. 2008; 47(5): 297-321
Butler JM, Begg EJ
The question of whether metabolic drug clearance is decreased in elderly people has been the subject of considerable debate and is very important because clearance is a determinant of dosing. Drug clearance has been shown to be consistently impaired for flow-limited (high-clearance) drugs, but there have been conflicting results for capacity-limited (low-clearance) drugs. A limitation of the studies of capacity-limited drugs is that most have estimated clearance based on total drug concentrations (protein-bound plus free). Total drug clearance reflects both the intrinsic clearance of free drug and the extent of protein binding. Total clearance is a valid measure for capacity-limited drugs with low protein binding and appears to be consistently impaired in elderly subjects. For phenazone [antipyrine] (fraction unbound [f(u)] >0.9), seven studies have demonstrated statistical reductions in clearance of 20-52%. For theophylline (f(u) 0.6), five studies have demonstrated reductions in clearance of 22-35%. For paracetamol [acetaminophen] (f(u) 0.8), the clearance of which has been quoted as unchanged, four studies have demonstrated reductions in clearance of 19-35%. For highly protein-bound drugs, total clearance is not the appropriate parameter. Free drug clearance is more appropriate since it is independent of changes in protein binding. The literature was reviewed to test the hypothesis that in elderly people, capacity-limited drugs with high protein binding will show decreased free clearance even in the absence of a decrease in total clearance. For these drugs, data for free drug clearance based on measurement of actual free drug concentrations are limited, but suggest that the intrinsic metabolic clearance is impaired in elderly subjects. Four studies of naproxen (f(u)
J Pharm Sci. 2008 Apr 8;
Di Martino P, Malaj L, Censi R, Martelli S
In the present work, authors produced tablets of anhydrous sodium naproxen by wet granulation using a high-shear mixer-granulator. Drug hydrated to the tetrahydrated form, as observed by X-ray powder diffractometry. After wet granulation, authors then performed two different drying procedures, obtaining granules of different water content and crystallographic characteristics. The first procedure dried granules in the high-shear mixer-granulator by applying vacuum at room temperature (batch A), while the second employed the same apparatus and time, under vacuum at 40 degrees C (batch B). X-ray powder diffractometry revealed that the sodium naproxen (SN) contained in batch A granules was a mixture of dihydrated and tetrahydrated forms (as demonstrated by the coexistence of peaks typical of both hydrated forms), while that of batch B granules was a mixture of monohydrated and tetrahydrated forms. This means that differences in drying procedures could lead to products of different crystallographic properties. The behavior under compression was evaluated, revealing that batch A offered the best tabletability and compressibility. These results make it possible to conclude that differences in the crystallographic properties and water content of SN are such that different hydration/drying processes can alter the drug crystal form and thus the tabletability of the resulting granules. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci.
Impact of naproxen sodium at over-the-counter doses on cyclooxygenase isoforms in human volunteers.
Int J Clin Pharmacol Ther. 2008 Apr; Volume 46(April): 180-186
Hinz B, Cheremina O, Besz D, Zlotnick S, Brune K
Objective: Over the last few years, there has been concern regarding the cardiovascular safety of selective cyclooxygenase (COX)-2 inhibitors and high-dose regimens of nonsteroidal anti-inflammatory drugs (NSAIDs). On the other hand, those compounds which elicit an almost complete (> 95%) and continuous suppression of platelet COX-1 may represent an exception. Apart from aspirin, which irreversibly inactivates COX-1, high-dose naproxen causes sustained COX-1 inhibition throughout the dose interval in some individuals. The present study examines whether naproxen sodium after a single dose administration and at steady state using âover-the-counter (OTC) dosesâ produces sufficient COX-1 inhibition. COX-2 inhibition was assessed concomitantly. Methods: Ex vivo inhibition of COX enzymes and the pharmacokinetics of naproxen were assessed in four volunteers receiving 220 mg naproxen sodium b.i.d. for 7 days. Blood samples were obtained pre-dose, at specified time points after the first dose on Day 1, and 12 hours after the previous evening dose on Days 2, 3, 4, 5 and 8. Recovery was assessed up to 36 hours after the last dose. Coagulation-induced thromboxane B2 formation and lipopolysaccharide-induced prostaglandin E2 synthesis were measured ex vivo in human whole blood as indices of COX-1 and COX-2 activity. Results: Maximal inhibition after a single dose and at steady state were as follows: 94% and 93% (COX-1), and 79% and 85% (COX-2). A greater than 95% COX-1 inhibition was observed transiently in 2 of 4 volunteers at the time of maximal plasma concentration after a single-dose administration and in 1 of 4 volunteers throughout the 12-hour dose interval at steady state. For both isoenzymes, COX inhibition correlated with naproxen plasma levels (ex vivo IC50 values of 35.48 Amicromol/l (COX-1) and 64.62 Amicromol/l (COX-2)). Conclusions: Administration of naproxen sodium at OTC doses was associated with a profound inhibition of both COX enzymes. Although low-dose naproxen may elicit a virtually complete COX-1 inhibition in some individuals, it does not mimic the reliable, sustained and complete COX-1 blockade produced by aspirin. In conclusion, prolonged treatment with 220 mg naproxen sodium b.i.d. is not expected to provide sufficient cardioprotection in all patients, but may influence platelet function in some.
J Biochem Biophys Methods. 2008 Apr 24; 70(6): 889-96
El-Enany N, Belal F, Rizk M
The alternating current (AC(t)) polarographic behavior of lansoprazole (LNS) and omeprazole (OMP) was studied in Britton Robinson buffers (BRb) over the pH range 4.1-11.5. In BRb of pH 9.6 and 10.5, well-defined AC(t) peaks were obtained for both LNS and OMP, respectively. The current-concentration plots were rectilinear over the ranges of 0.4-20 microg mL(-1) and 0.2-10 microg mL(-1) for LNS and OMP respectively. The minimum detection limits (S/N=2) were 0.02 microg mL(-1) (5.4x10(-8) M) and 0.01 microg mL(-1) (2.9x10(-8) M) for LNS and OMP, respectively. The proposed method was successfully applied to the analysis of the two drugs in their commercial capsules. The average percent recoveries were favorably compared to those obtained by reference methods. Co-administered drugs such as naproxen and methotrexate did not interfere with the proposed method. The proposed method was further extended to the in-vitro determination of the lansoprazole in spiked plasma, the percentage recoveries was 98.47+/-1.29 (n=4). The pathway for the electrode reaction for both drugs involved reduction of the sulphonyl group into the corresponding thiol group at the Dropping Mercury Electrode. The advantages of the method were time saving and more sensitive than the other published voltammetric method. Yet The present study is the first report on the use of alterating current polarography (AC(t)) in this respect.
Management of chronic musculoskeletal pain in the Elderly: Opinions on oral medication use.
Inflammopharmacology. 2008 Apr; 16(2): 53-75
Kean WF, Rainsford KD, Kean IR
The use of oral medication in the treatment of chronic musculoskeletal pain in the elderly requires careful selection of drugs to control pain with consideration for both the physiological state and the presence of disease(s). Recent advances have improved the understanding of biomolecular mechanisms of chronic pain. These include the production of powerful pro-inflammatory cytokines by glial and microglial cells, which then lead to activation of major pain pathways from the periphery through the dorsal horn and supra-spinal pathways to the somatosensory and other higher cortical centres. This has allowed better recognition for intervention with anti-inflammatory agents to control cytokine production (e. g. prednisolone, triamcinolone and other brain-penetrating corticosteroids). Advances in understanding of chronic pain have lead to recognition of neuronal PX2 puringergic receptors as potential sites for drugs to control pain by more selective actions. Pain control in the elderly involves extensive use of analgesics, among them the non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), and various narcotics. Each of these has its drawbacks, mostly related to potential toxicities. Attempts to reduce the serious gastro-intestinal (GI) adverse effects of the NSAIDs by the introduction of the highly selective COX-2 inhibitors (coxibs) have only had limited benefit in reducing these untoward actions. Moreover, the risks of serious cardiovascular (CV) and renal side-effects, though statistically infrequent, are none the less of major concern. Cardio-renal effects have been attributed to some (e. g. diclofenac), but not all (e. g. naproxen) conventional NSAIDs. Here we make recommendations for a selection of certain NSAIDs to be used for pain therapy in the elderly in consideration of their relative safety and pharmacokinetics. While newer formulations of narcotics have given some advance in pain control, the application of this group of drugs requires close supervision in the elderly, especially those with cognitive decline, since drug actions on the central and peripheral nervous systems (CNS, PNS) can result in significant adverse effects of these agents (e. g. constipation, drowsiness, respiratory and cardiovascular decline).Improvements in the safety and effectiveness of musculoskeletal pain therapy in the elderly can only be achieved by identification and frequent re evaluation of the cause of the chronic pain and the impact on the patient's general medical state.