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Annals of Internal Medicine Dec 2023Li RHW, Lo SST, Gemzell-Danielsson K, et al. Lancet. 2023;402:851-858. 37597523. (Randomized Controlled Trial)
Randomized Controlled Trial
Li RHW, Lo SST, Gemzell-Danielsson K, et al. Lancet. 2023;402:851-858. 37597523.
Topics: Humans; Levonorgestrel; Contraception, Postcoital; Piroxicam; Double-Blind Method; Ethnicity
PubMed: 38048581
DOI: 10.7326/J23-0098 -
ACS Omega Nov 2023Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation, joint tissue damage, pain, and synovitis. It leads to deformity of joints,...
Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation, joint tissue damage, pain, and synovitis. It leads to deformity of joints, disability, and even premature death. Markers of inflammation are highly expressed in synovium fluid and serum of arthritic patients and play an important role in the pathophysiology of RA. These transcription factors promote the fabrication of type I interferons and inflammatory cytokines. In RA, degradation of synovial cartilage and bone results from stimulation of proinflammatory cytokines. Citronellol (Ct), a monoterpene alcohol, is found in citrus fruits and essential oils of many aromatic plants. It possesses numerous pharmacological properties such as antioxidant activity and potential antinociceptive and anti-inflammatory effects. Keeping in view the significant anti-inflammatory role of Ct, a trial of 28 days was conducted. Ct was administered orally at three different doses (25, 50, and 100) mg/kg in Freund's adjuvant-induced arthritic rats, and the results were compared with piroxicam, chosen as the standard drug. The antiarthritic activity of the compound was evaluated through measurements of arthritic scoring and plethysmometry before and after treatment. The blood biochemical and hematological parameters and histopathological analyses were performed. Additionally, qPCR was conducted to analyze the mRNA expression levels of TNF-α, IL-1β, NF-κB, MMP3, IL-6, and IL-4 in the blood. ELISA was performed to evaluate the levels of PGE2. The results demonstrated that Ct showed significant results at all doses, but the highest dose proved to be most significant in terms of decreasing arthritic scoring and paw edema, indicating the antiarthritic potential of Ct. Furthermore, the compound was found to downregulate all the proinflammatory cytokines (TNF-α, IL-1β, NF-κB, MMP3, and IL-6) and upregulate the anti-inflammatory cytokine (IL-4). The levels of PGE2 were also reduced which further supported the antiarthritic effects of Ct and validated it as a potential antiarthritic candidate.
PubMed: 38046326
DOI: 10.1021/acsomega.3c06374 -
European Journal of Pharmacology Dec 2023Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve various symptoms such as headache, arthralgia, and dental pain. While the primary mechanism of...
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve various symptoms such as headache, arthralgia, and dental pain. While the primary mechanism of NSAID-based pain relief is the inhibition of cyclooxygenase-2, several NSAIDs also modulate other molecular targets related to nociceptive transmission such as voltage-gated Na channels. In the present study, we examined the effects of NSAIDs on persistent Na current (I) mediated by tetrodotoxin-resistant (TTX-R) Na channels in small-to medium-sized trigeminal ganglion neurons using a whole-cell patch-clamp technique. At clinically relevant concentrations, all propionic acid derivatives tested (ibuprofen, naproxen, fenoprofen, and flurbiprofen) preferentially inhibited the TTX-R I. The inhibition was more potent at acidic extracellular pH (pH 6.5) than at normal pH (pH 7.4). Other NSAIDs, such as ketorolac, piroxicam, and aspirin, had a negligible effect on the TTX-R I. Ibuprofen both accelerated the onset of inactivation and retarded the recovery from inactivation of TTX-R Na channels at acidic extracellular pH. However, all NSAIDs tested in this study had minor effects on voltage-gated K currents, as well as hyperpolarization-activated and cyclic nucleotide-gated cation currents, at both acidic and normal extracellular pH. Under current-clamp conditions, ibuprofen decreased the number of action potentials elicited by depolarizing current stimuli at acidic (pH 6.5) extracellular pH. Considering that extracellular pH falls as low as 5.5 in inflamed tissues, TTX-R I inhibition could be a mechanism by which ibuprofen and propionic acid derivative NSAIDs modulate inflammatory pain.
Topics: Rats; Animals; Tetrodotoxin; Ibuprofen; Trigeminal Ganglion; Sodium Channels; Sodium Channel Blockers; Rats, Sprague-Dawley; Membrane Potentials; Anti-Inflammatory Agents, Non-Steroidal; Neurons; Pain; Acids; Hydrogen-Ion Concentration
PubMed: 37992887
DOI: 10.1016/j.ejphar.2023.176218 -
Zhongguo Zhen Jiu = Chinese Acupuncture... Sep 2023This study systematically reviewed the clinical efficacy of acupuncture for lumbar myofascial pain syndrome. The randomized controlled trials (RCTs) regarding... (Meta-Analysis)
Meta-Analysis
This study systematically reviewed the clinical efficacy of acupuncture for lumbar myofascial pain syndrome. The randomized controlled trials (RCTs) regarding acupuncture for lumbar myofascial pain syndrome were searched in PubMed, Cochrane Library, Web of Science, EMbase, Scopus, China national knowledge infrastructure (CNKI), Wanfang database, VIP database, and China biomedical literature service system (SinoMed) from database inception until August 1st, 2022. The Cochrane's risk of bias assessment tool was used to assess the risk of bias in all included studies, and Review Manager 5.3 software was used for statistical analysis of the extracted data. As a result, 12 RCTs, involving 1 087 patients with lumbar myofascial pain syndrome, were ultimately included. The Meta-analysis results showed that the visual analog scale (VAS) score of pain in the observation group was lower than those in the oral non-steroidal anti-inflammatory medication control [=-1.67, 95% (-2.44, -0.90), =4.26, <0.000 1] and other treatment control [low-frequency electrical stimulation, , electromagnetic wave irradiation combined with piroxicam gel, =-1.98, 95% (-2.48, -1.48), =7.74, <0.000 01]. The pain rating index (PRI) score in the observation group was lower than those in the lidocaine injection control [=-2.17, 95% (-3.41, -0.93), =3.44, =0.000 6] and other treatment control [low-frequency electrical stimulation, , =-5.75, 95% (-9.97, -1.53), =2.67, =0.008]. The present pain intensity (PPI) score in the observation group was lower than that in other treatment control [low-frequency electrical stimulation, , =-1.04, 95% (-1.55, -0.53), =4.01, <0.000 1]. In conclusion, compared with oral non-steroidal anti-inflammatory medication, low-frequency electrical stimulation, , and electromagnetic wave irradiation combined with piroxicam gel, acupuncture is more effective in reducing pain in patients with lumbar myofascial pain syndrome; acupuncture also exhibites advantage over lidocaine injection in improving PRI score and showed better outcomes over and low-frequency electrical stimulation in improving PRI and PPI scores.
Topics: Humans; Piroxicam; Acupuncture Therapy; Pain; Myofascial Pain Syndromes; Anti-Inflammatory Agents, Non-Steroidal; Lidocaine
PubMed: 37986258
DOI: 10.13703/j.0255-2930.20221120-0002 -
The Journal of Headache and Pain Nov 2023Medication overuse headache (MOH) is a secondary headache that accompanies chronic migraine. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequently used...
OBJECTIVE
Medication overuse headache (MOH) is a secondary headache that accompanies chronic migraine. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequently used analgesics worldwide and they are known to induce leaky gut. In this study, we aimed to investigate whether NSAID induced MOH is associated with altered circulating lipopolysaccharide binding protein (LBP) levels and inflammatory molecules.
MATERIALS AND METHODS
Piroxicam (10 mg/kg/day, po) for 5 weeks was used to induce MOH in female Sprague Dawley rats. Pain behavior was evaluated by periorbital withdrawal thresholds, head-face grooming, freezing, and head shake behavior. Serum samples and brain tissues were collected to measure circulating LBP, tight junction protein occludin, adherens junction protein vascular endothelial (VE)-cadherin, calcitonin gene-related peptide (CGRP), IL-6 levels and brain high mobility group box-1 (HMGB1) and IL-17 levels.
RESULTS
Chronic piroxicam exposure resulted in decreased periorbital mechanical withdrawal thresholds, increased head-face grooming, freezing, and head shake behavior compared to vehicle administration. Serum LBP, CGRP, IL-6, IL-17, occludin, VE-cadherin levels and brain IL-17 and HMGB1 levels were significantly higher in piroxicam group compared to controls. Serum LBP was positively correlated with occludin (r = 0.611), VE-cadherin (r = 0.588), CGRP (r = 0.706), HMGB1 (r = 0.618) and head shakes (r = 0.921), and negatively correlated with periorbital mechanical withdrawal thresholds (r = -0.740).
CONCLUSION
Elevated serum LBP, VE-cadherin and occludin levels indicating disrupted intestinal barrier function and leakage of LPS into the systemic circulation were shown in female rats with MOH. LPS induced low-grade inflammation and elevated nociceptive and/or pro-inflammatory molecules such as HMGB1, IL-6, IL-17 and CGRP may play a role in the development and maintenance of MOH. Interference with leaky gut and pro-inflammatory nociceptive molecules could also be a target for sustained management of MOH.
Topics: Rats; Female; Animals; Lipopolysaccharides; Calcitonin Gene-Related Peptide; HMGB1 Protein; Interleukin-17; Rats, Sprague-Dawley; Piroxicam; Occludin; Interleukin-6; Headache Disorders, Secondary; Anti-Inflammatory Agents, Non-Steroidal
PubMed: 37940864
DOI: 10.1186/s10194-023-01672-4 -
Annales Pharmaceutiques Francaises May 2024This investigation aimed to explore the potential of non-ionic surfactant based niosomal vesicles encapsulating tenoxicam (TN; anti-rheumatic drug) for the treatment of...
OBJECTIVE
This investigation aimed to explore the potential of non-ionic surfactant based niosomal vesicles encapsulating tenoxicam (TN; anti-rheumatic drug) for the treatment of rheumatic diseases.
MATERIAL AND METHODS
Mechanical dispersion technique with controlled pressure was employed to prepare different niosomal formulations. The effects of different ratios of surfactant (span-60), lipid, and sodium deoxycholate on noisome's physicochemical properties have been examined. Moreover, inhibition of TNF-α in lipopolysaccharide-activated cultured Human leukemia monocytic (THP-1) cells were demonstrated to assess the in vitro inflammation profile. Finally, the optimized niosomal formulation (TN3) was prepared in gel matrix consist of carbopol 934 (termed as TN34) and stability was also tested at 4±2 ̊C, 25±2 ̊C, 37±2 ̊C and 45±2 ̊C for 6 months.
RESULTS
The optimized niosomal formulation exhibited a small vesicle size (165±14nm) and high drug encapsulation (79.64±1.5%). Niosomal gel formulation TN34 showed pH (6.7), viscosity (6810±3.34 cps), spreadability (19.11±1.87gm.cm/sec) and also displayed sustained release pattern of drug release (98.16±0.07% TN released from gel matrix in 24h) in vitro release study. TN34 exhibited substantial anti-inflammatory response, with ∼75% inhibition of TNF-α in 48h. Stability investigation revealed that refrigerator temperature is most suitable for the storage of niosomal gel.
CONCLUSION
Transdermal niosomal formulation displayed promising potential in the treatment of rheumatic diseases.
Topics: Humans; Liposomes; Tumor Necrosis Factor-alpha; Piroxicam; Surface-Active Agents; Particle Size
PubMed: 37923009
DOI: 10.1016/j.pharma.2023.10.010 -
Pharmaceutical Research Oct 2023New solutions are needed to enable the efficient use of poorly water-soluble drugs. Therefore, we aimed to demonstrate that decreasing particle size with a...
PURPOSE
New solutions are needed to enable the efficient use of poorly water-soluble drugs. Therefore, we aimed to demonstrate that decreasing particle size with a solution-to-particle method known as nanoforming can improve dissolution and thus bioavailability.
METHODS
Piroxicam, a poorly water-soluble non-steroidal anti-inflammatory drug (NSAID), was used as a model compound. A Quality-by-Design (QbD) approach was used to nanoform piroxicam and a design space was established. The pharmacokinetics of piroxicam nanoparticles were compared to two marketed products in a clinical trial.
RESULTS
Nanoformed tablets showed a 33% increase in exposure during the first hour after dosing (AUC) compared with an immediate release tablet and was similar to a fast absorbing tablet incorporating complexation of piroxicam with β-cyclodextrin.
CONCLUSIONS
The results show that nanoforming enabled more rapid absorption in comparison to a typical marketed tablet and indicate that nanoforming is an alternative to complex formulation such as cyclodextrins based products. The study outcomes support the potential of nanoforming for producing fast-acting dosage forms of poorly soluble drugs.
Topics: Piroxicam; Anti-Inflammatory Agents, Non-Steroidal; Cyclodextrins; Tablets; Water; Solubility
PubMed: 37910340
DOI: 10.1007/s11095-023-03624-8 -
Pharmaceutics Oct 2023Lipid and/or polymer-based drug conjugates can potentially minimize side effects by increasing drug accumulation at target sites and thus augment patient compliance....
Lipid and/or polymer-based drug conjugates can potentially minimize side effects by increasing drug accumulation at target sites and thus augment patient compliance. Formulation factors can present a potent influence on the characteristics of the obtained systems. The selection of an appropriate solvent with satisfactory rheological properties, miscibility, and biocompatibility is essential to optimize drug release. This work presents a computational study of the effect of the basic formulation factors on the characteristics of the obtained in situ-forming particulates (IFPs) encapsulating a model drug using a 2.3 full factorial experimental design. The emulsion method was employed for the preparation of lipid and/or polymer-based IFPs. The IFP release profiles and parameters were computed. Additionally, a desirability study was carried out to choose the optimum formulation for further morphological examination, rheological study, and PBPK physiological modeling. Results revealed that the type of particulate forming agent (lipid/polymer) and the incorporation of structure additives like Brij 52 and Eudragit RL can effectively augment the release profile as well as the burst of the drug. The optimized formulation exhibited a pseudoplastic rheological behavior and yielded uniformly spherical-shaped dense particulates with a PS of 573.92 ± 23.5 nm upon injection. Physiological modeling simulation revealed the pioneer pharmacokinetic properties of the optimized formulation compared to the observed data. These results assure the importance of controlling the formulation factors during drug development, the potentiality of the optimized IFPs for the intramuscular delivery of piroxicam, and the reliability of PBPK physiological modeling in predicting the biological performance of new formulations with effective cost management.
PubMed: 37896273
DOI: 10.3390/pharmaceutics15102513 -
European Journal of Pharmaceutics and... Dec 2023Intestinal drug solubility is a key parameter controlling absorption after the administration of a solid oral dosage form. The ability to measure fed state solubility in...
Intestinal drug solubility is a key parameter controlling absorption after the administration of a solid oral dosage form. The ability to measure fed state solubility in vitro is limited and multiple simulated intestinal fluid recipes have been developed but with no consensus which is optimal. This study has utilised nine bioequivalent simulated fed intestinal media recipes that cover over 90% of the compositional variability of sampled fed human intestinal fluid. The solubility of 24 drugs (Acidic; furosemide, ibuprofen, indomethacin, mefenamic acid, naproxen, phenytoin, piroxicam, valsartan, zafirlukast: Basic; aprepitant, atazanavir, bromocriptine, carvedilol, dipyridamole, posaconazole, tadalafil: Neutral; acyclovir, carbamazepine, felodipine, fenofibrate, griseofulvin, itraconazole, paracetamol, probucol) has been assessed to determine if structured solubility behaviour is present. The measured solubility behaviour can be split into four categories and is consistent with drug physicochemical properties and previous solubility studies. For acidic drugs (category 1) solubility is controlled by media pH and the lowest and highest pH media identify the lowest and highest solubility in 90% of cases. For weakly acidic, basic and neutral drugs (category 2) solubility is controlled by media pH and total amphiphile concentration (TAC), a consistent solubility pattern is evident with variation related to individual drug media component interactions. The lowest and highest pH × TAC media identify the lowest and highest solubility in 70% and 90% of cases respectively. Four drugs, which are non-ionised in the media systems (category 3), have been identified with a very narrow solubility range, indicating minimal impact of the simulated media on solubility. Three drugs exhibit solubility behaviour that is not consistent with the remainder (category 4). The results indicate that the use of two bioequivalent fed intestinal media from the original nine will identify in vitro the maximum and minimum solubility values for the majority of drugs and due to the media derivation this is probably applicable in vivo. When combined with a previous fasted study, this introduces interesting possibilities to measure a solubility range in vitro that can provide Quality by Design based decisions to rationalise drug and formulation development. Overall this indicates that the multi-dimensional media system is worthy of further investigation as in vitro tool to assess fed intestinal solubility.
Topics: Humans; Solubility; Hydrogen-Ion Concentration; Intestines; Pharmaceutical Preparations; Indomethacin; Intestinal Absorption
PubMed: 37890541
DOI: 10.1016/j.ejpb.2023.10.017 -
Pakistan Journal of Pharmaceutical... Sep 2023Stellaria media L. has traditionally been used to treat inflammatory and gastrointestinal ailments. This study aimed to phytochemically characterize the S. media extract...
Stellaria media L. has traditionally been used to treat inflammatory and gastrointestinal ailments. This study aimed to phytochemically characterize the S. media extract and explore its anti-ulcer efficacy against piroxicam-induced stomach lesions in Wistar rats. Phytochemical analysis was performed and antioxidant capacity of extract was determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. In vivo, piroxicam (30mg/kg) was administered to induce gastric ulceration. Gastro protective effect of S. media extract was observed at 150, 300 and 450mg/kg, respectively. While omeprazole (20mg/kg) was used as a conventional anti-ulcer drug. After oral treatment for 14 days, stomach acidic secretions, ulcerogenic indices, hematological markers and oxidative stress parameters were assessed along with histological examination. The existence of polyphenol contents in S. media extract was confirmed in correlation to a marked DPPH inhibition (IC 27.94µg/mL). S. media extract resulted in a dose-dependent elevation in gastric pH while a decrease in acid volume, acidity and ulceration. Also, S. media extract administration restored the impaired hematological markers (RBCs, Hb, WBCs and PLTs) and decreased oxidative stress by reducing oxidants (TOS and MDA) while raising antioxidants (TAC and CAT). Furthermore, gastric histological results corroborated the aforementioned findings. Conclusively, S. media could provide a promising protective effect against drug-induced gastric ulceration.
Topics: Rats; Animals; Stomach Ulcer; Piroxicam; Rats, Wistar; Methanol; Stellaria; Plant Extracts; Phytotherapy; Antioxidants; Anti-Ulcer Agents; Phytochemicals; Gastric Mucosa
PubMed: 37869918
DOI: No ID Found