International Journal of Research in Clinical Medicine and Pharmacy Practice.

2018;1(1) pg 13-20

International Journal of Research in Clinical

Medicine and Pharmacy Practice
Available online at https://ijrcmpp.com

SYSTEMATIC REVIEW ARTICLE

Meta-analytical Research and Therapeutic Efficacy of Meloxicam in Arthritis

Adarsh K. Pathak*

*Kunwar Hari Bansh Singh College of Pharmacy, Jaunpur (U.P)

IJRCMPP 2018; 1(1); pp. 13-20

CCorresponding Author: Adarsh K. Pathak
Received: May 3, 2018
A Address: Kunwar Hari Bansh Singh College of Pharmacy, Jaunpur (U.P)
Accepted: May 24, 2018 E-mail: akp7779@gmail.com
Published: May 25, 2018

ABSTRACT:
Objective: In this systematic review and meta-analysis, we estimate the
effectiveness and safety of the patient with arthritis condition who has treated with
meloxicam (ML) therapy.
Methods: A systematic review of the literature accomplished with PRISMA
guidelines. We carried out a report search on the Medline and Cochrane databases
published from 01 January 1999 up to 31 March 2018. We used the text word and
the medical subject heading term (Mesh term) ‘meloxicam’, ‘meloxicam and
arthritis’. Inclusion criteria based on RCTs, all age minimum 14 days duration
therapy, English as reported language, in-vivo human trail while exclusion criteria
based on the review, editorials, non- randomized, case study, observational study,
pharmacokinetic study, in-vitro trail and studies lacking measurable results. The
total number of participants in the meta-analysis was 426 and age range 18-75
years. Usually, dose range in ML therapy was 7.5 mg/day to 15 mg/day divided into
one, two, and thrice daily doses, whereas one study included a combination as
meloxicam and pregabalin and duration of treatment was 14 to 168 days.
Result: The literature search on the Medline databases resulted in 42 and
Cochrane databases resulted in 411 papers, after reading 22 papers removed
because duplicates papers, 422 papers excluded by exclusion criteria, 4 papers
exclude because fewer efficacies in studies, and 05 papers selected for meta-
analysis and identified. In selected studies involved 03 studies on osteoarthritis, 01
study on kashin beck disease and 01 study on arthritis with muscular pain. The
meta-analysis indicated that there was a statistically significant in the rate of
clinical failure 7.04% (fixed effect model OR [0.8540], 95%-CI [0.8122; 0.8878] and
random effect model OR [0.8573], 95%-CI [0.7315; 0.9298]) for ML therapy and
heterogeneity also evaluated in the overall study (rate of failure: Q [27.22], I2
[85.3%], P [< 0.01]).

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 International Journal of Research in Clinical Medicine and Pharmacy Practice. 2018;1(1) pg 13-20

Conclusion: The inadequate quantities of data from this evidence-based

systematic review and meta-analysis showed the result ML towards effective in
arthritis condition further reduce pain, and bone stiffness. The selected literature
concerning the results of the clinical efficacy of this meta-analysis, ML is a good
alternative for those using an arthritis condition.
KEYWORDS: Meloxicam, Rheumatoid Arthritis, Osteoarthritis, Kashin-Beck Disease, Meta Analysis

INTRODUCTION:
Meloxicam1-7 (ML) associated with a group of drug, known as the non-selective anti-
inflammatory drug8-9 (NSAID) which originated from enolic acid. 10 It is chemically as
4-hydroxy-2-methyl-N-(5-methyl-2- tiazolil)-2H-1,2-benzotiacina-3-carboxamide-1,1-
dioxide (Figure-1) which more potent COX-2 11-12 and sometimes COX-113-15 inhibitor.16-
17
The chemical structure of ML following below. 18 NSAIDs are valuable agents and
most commonly used medications in the world. 19-20 ML is well absorbed from the GIT
that bound to albumin, which has an oral bioavailability of 80%, Cmax achieved
within 4 to11 hours and elimination half-life 13 to 20 hours 21 in which once daily
dosing medication formed better efficacy. 22 ML inhibit the function of prostaglandin-
endoperoxide synthase (PTGS),23 it formed two isozymes. These isozymes are
PTGS1 and PTGS2,24 which are known as "prostaglandin synthase (PHS)", and
"prostaglandin-endoperoxide synthetase (PES)", sometimes refers to COX-1 and
COX-2.25-26 COX-2 inhibitors, which are safer than other NSAIDs, which are used to
induced adverse effect gastrointestinal,27-28 significantly increasing the risk of gastric
hemorrhage.29-30 ML use to terminate acute and chronic inflammatory painful
disorders like arthritis, postoperative pain, and dental pain, 31-32 in there the most
common form of arthritis are rheumatoid arthritis ,33-36 (RA) and osteoarthritis (OA).37
OA is characterizing by joint pain and stiffness, which produces a possible effect on
muscular atrophy and bone distortion 38-39 mainly knee osteoarthritis (KOA). Chronic
severe skeletal distortion and dwarfism osteochondropathy is the kashin-beck
disease (KBD) and most frequently affected sites are the distal limb joints. 40 In OA
most affected middle to elderly aged people and reducing daily living activities in
there women maximum affected because of her overweight. 41 Inflammatory arthritis
known as gout and is characterized by deposition of monosodium urate crystals in
joints and other tissues, in there is more common in men over the age of 40
years.42 ML is safe to use but sometimes-produced unwanted side effects such as
gastrointestinal damage43-44, platelet inhibition, and renal impairment. These side
effects produced by COX-1 and COX-2 inhibition; majorly intolerance symptoms are
also reported as cutaneous-mucous (urticaria/angioedema) or respiratory
(rhinitis/asthma) when patient undergo long-term therapy with ML. 45-46 ML is well
tolerated similar to other NSAIDs, which associated with increased risk of
gastrointestinal.47-48 ML also used as standard antithrombotic therapy with low-
molecular-weight heparin and aspirin.49 It was also reported that single
subcutaneous dose of ML was as clinically effective as up to 3 consecutive daily
intravenous doses of flunixin meglumine when used as an adjunctive therapy to
antibacterial and anti fungal therapy in the treatment of acute febrile respiratory
disease especially with doxofylline50-70
The systematic review is multi-step process aimed to determine all accessible and
valid literature concerning a specific problem, to evaluate their reliability and to
systematize accessible data in a qualitative or quantitative (meta-analysis)
procedure.50

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 International Journal of Research in Clinical Medicine and Pharmacy Practice. 2018;1(1) pg 13-20

Figure 1 Chemical structure of meloxicam

MATERAIL AND METHOD:
Literature search and eligibility of trials:
A systematic review concern certain literature accomplished with PRISMA
guidelines.51-52 We carried out a report search on the Cochrane and Medline
databases for selectable randomized controlled trials (RCTs) considering both sex
including subjects published from 1 January 1999 up to 31 March 2018. We used the
text word and the medical subject heading term (Mesh term) ‘meloxicam',
‘meloxicam and arthritis'. Inclusion criteria based on RCTs, all age minimum 14 days
duration therapy, English as reported language, in-vivo human trail while exclusion
criteria based on the review, editorials, non- randomized, case study, observational
study, pharmacokinetic study, in-vitro trail and studies lacking measurable results.
The literature search as first mesh term ‘meloxicam’ on the Medline databases
resulted in 33 and Cochrane databases resulted in 347 papers, and second mesh
term ‘meloxicam and arthritis on the Medline databases resulted in 09 and
Cochrane databases resulted in 64 papers. After reading 22 papers removed
because duplicates papers, 422 papers excluded by exclusion criteria, 4 papers
exclude because fewer efficacies in studies, and 05 papers selected for meta-
analysis and identified. In selected studies, involve 03 studies on osteoarthritis, 01
study on kashin beck disease and 01 study on arthritis with muscular pain. Two
prosecutors followed by the third independently determined the inclusion criteria
and validation of the studies.
Primary outcome:
The primary result was the clinical failure rate in the association of subjects treated
by ML therapy. We prefer as a time for assessment of the clinical outcome the day
proximate to day 5. All studies carried out primary outcome evaluations between 14
to 168 days and dose range in ML therapy was 7.5 mg/day to 15 mg/day divided
into one, two, and thrice daily doses, whereas one study included a combination as
meloxicam and pregabalin.
Data extraction:
From the various trial report, we extricate data on the year, inclusion and exclusion
criteria, ML therapy used in association (class, dose, and duration), patient
demographics (age and gender), number of subjects allotted per treatment, number
of patients eligible for the efficacy analysis.
Statistical analysis:
We calculated odds ratios (OR) and their 95% confidence intervals (CI) for clinical
failures as efficacy. Within and between-study variance and heterogeneity were
exactly evaluated by RR, Q, P, I2 and two-tailed P value. We used DerSimonian–
Laird random effects models for meta-analysis and calculated by R version 3.5.0
(RStudio version 1.1.453) software.
RESULT:
Literature search, eligible and excluded studies:

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 International Journal of Research in Clinical Medicine and Pharmacy Practice. 2018;1(1) pg 13-20

We carried out a literature search of the Medline and Cochrane databases from 1
January 1999 to 31 March 2018. During the systematic review, five studies that
suitable the maximal eligibility criteria established for this meta-analysis were
identified and selected.25,40,53,54,38 The PRISMA for systematic literature review
confines of the inclusion and exclusion criteria for the studies presented in Figure 2.
The specify articles have been evaluated by subgroups according to the introduction
of data from the original study. The table for systematic literature review confirms
the distinctions and results of the involved studies presented in Table 1. The studies
comprise the total number of patients 426 (Highest number of population in one
study was 144, median 72 and lowest 32) randomized patients of all age group was
18 to 83 years and duration of treatment was 14 to 168 days. The studies further
divided into three groups according to dose frequency (3 studies in 7.5 mg/day, 1
study in 10mg/day, and 1 study in 15mg/day) to evaluate efficacy associated with
dose frequency; whereas one study included a combination of meloxicam and
pregabalin.
Meta-analysis:
The decision estimate carried out to cover 426 patients of five selected studies on
the numbers, which take duration between 14 to 168 days. Overall, there were
clinical failures 7.04% (fixed effect model OR [0.8540], 95%-CI [0.8122; 0.8878] and
random effect model OR [0.8573], 95%-CI [0.7315; 0.9298]) evaluable patients in
the ML treatment arm. Heterogeneity also evaluated in the overall study (rate of
failure: Q [27.22], I2 [85.3%], P [< 0.01]). We also analyzed dose frequency with
clinical efficacy (rate of failure). Features and events of estimated OR among 95%-CI
indicated in figure 3. The estimates showed ML in the rate of clinical efficacy.
DISCUSSION:
The meta-analysis showed that the rate of failure for ML therapy was 7.04%. The
paucity of data favors ML therapy if dose frequency for applied between the range
of 7.5 to 15 mg/day. Before discussing the results in more detail, it is important to
note that the greatest strength of the study lies in the inherent design features. The
fact that it done through a systematic review and included the use of statistical
methods such as meta-analysis, allows us to say that until March 2018. This is the

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 International Journal of Research in Clinical Medicine and Pharmacy Practice. 2018;1(1) pg 13-20

synthesis of the

Figure 2 Flowchart of the process of the systematic literature review with inclusion and exclusion criteria

evidence regarding the treatment of arthritis with ML. The overall results need to be
interpreted with caution, as biases cannot be excluded. We found no evidence of
overt publication bias or changes in the pooled treatment effect over time. Lack of
allocation concealment may also cause bias in this setting. However, it is significant
to focus some limitations of this analysis: 1) All studies have not reported a
standard dose, although most studies use the recommended doses for each drug, 2)
Although all studies underwent a quality assessment to control the overall technical
standardization, they individually exposed to methodological weaknesses.
Concerning the results of the clinical efficacy of this meta-analysis, the literature
findings confirmed, ML is a good alternative for those using an arthritis condition. As
for the duration of treatment, no difference between the shortened and the
standard therapy (14-168 days) observed.
CONCLUSION:
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 International Journal of Research in Clinical Medicine and Pharmacy Practice. 2018;1(1) pg 13-20

Analyzing particular events of this evidence-based systematic review and meta-

analysis, treatment with ML formed effective and satisfying by following
questionnaires.

Figure 3 Meta-analysis of clinical efficacy (rate of failure) of meloxicam therapy

Table 1 Outline extraction for clinical efficacy (rate of failure) and meloxicam therapy
S. Author Type of Diagnosis No. Age Gend Dose Durati Rate Side
N trial of er on of effect
o. patie failu
nt re
1 J. P Randomize Osteoarthriti 117 58 M-117 7.5 2 7 NA
Valat d, double- s yea mg/day weeks
2 Rui Luo Randomize Kashin-beck 72 18– F-119, 7.5 6 12 GIT

et.al.20 d, mono- disease 75 M-49 mg/day weeks disorder,

11 blind study yea headach

rs e,

dizziness

, fatigue,

edema

and skin

rash
3 Seiji Randomize Knee 61 50- F-63 , Meloxicam 4 12 Gastritis,

ohtori d osteoarthritis 83 M-26 - 10 weeks nausea,

et.al.20 prospectiv yea mg/day, dizziness

13 e study rs Pregabalin

- 25

mg/day
4 Arvind Randomize Musculoskele 32 45 - NA Meloxicam 24 12 Mild

chopra d and tal pain and 50 -7.5 weeks upper

et.al.20 parallel arthritis yea mg/day abdomin

14 efficacy rs al pain,

trial nausea
5 Tara Randomize Knee 144 35 - F-122, 15 mg/day 12 9 NA

Symond d, double- osteoarthritis 75 M- 22 week

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 International Journal of Research in Clinical Medicine and Pharmacy Practice. 2018;1(1) pg 13-20

s blind study yea

et.al.20 rs

15

The testimonials reviewed and detailed below:

1. Is meloxicam efficacious for severe arthritis condition?
Answer: Yes
Comments: Possible evidence declared the results of meloxicam therapy, which
are towards effective in arthritis, further is able to reduce the pain and bone
stiffness. The clinical efficacy of this meta-analysis, the literature findings
confirmed, that ML is a good alternative for those using an arthritis condition in
there once daily dosing medication formed better efficacy.

REFERENCE:
1. Nima M, Kotaji M, Khayrallah A, et.al. Preparation and evaluation of meloxicam solid dispersions
by solvent evaporation method. Int J Res Pharm. 2014;5(11):838-845. doi:10.7897/2230-
8407.0511172
2. Arantes Rodrigues R, Pinto Leite R, Fidalgo Goncalves L, et.al. Meloxicam synergistically
enhances the in vitro effects of sunitinib malate on bladder cancer cells. J Appl Biomed.
2013;11(2):79-92. doi:10.2478/v10136-012-0034-7
3. Distel M, Mueller C, Bluhmki E, et.al. Safety of meloxicam a global analysis of clinical trials. Br J
Rheumatol. 1996;35(Supplement1):68-77. http://www.ncbi.nlm.nih.gov/pubmed/8630641.
4. Kumar SG and Mishra DN. Analgesic anti inflammatory and ulcerogenic studies of meloxicam
solid dispersion in rodents. Iran J Pharmacol Ther. 2006;5(1):77-79.
doi:10.1358/mf.2006.28.7.1003549
5. Oliveira E, Azevedo R, Bonfilio R, et.al. Dissolution test optimization for meloxicam in the tablet
pharmaceutical form. Brazilian J Pharm Sci. 2009;45(1):67-73. doi:10.1590/S1984-
82502009000100008
6. Turck D, Roth W, Busch U, et.al. A review of the clinical pharmacokinetics of meloxicam.
Rheumatology. 1996;35(Supplement1):13-16. doi:10.1093/rheumatology/35.suppl_1.13
7. Yocum D, Fleischmann R, Dalgin P, et.al. Safety and efficacy of meloxicam in the treatment of
osteoarthritis A 12 week double blind multi dose placebo controlled trial. Arch Intern Med.
2000;160(19):2947-2954. doi:10.1001/archinte.160.19.2947
8. Akhilesh Gupta and Swati Rawat. Synthesis and anti inflammatory study of novel
fluorobenzothiazole derivatives. J. Chem. Pharm. Res. 2010;2(5):244-2589.
9. Panara MR, Renda G, Sciulli MG, et.al. Dose dependent inhibition of platelet cyclooxygenase 1
and monocyte cyclooxygenase 2 by meloxicam in healthy subjects. J Pharmacol Exp Ther.
1999;290(1):276-280.
http://www.ncbi.nlm.nih.gov/pubmed/10381787.
10. Lanocha Arendarczyk N, Baranowska Bosiacka I, Kot K, et.al. Expression and activity of
cyclooxygenase 1 and cyclooxygenase 2 in acanthamoeba infected lungs according to the host
immunological status. Int J Mol Sci. 2018;19(1):1-17. doi:10.3390/ijms19010121
11. Thomas L and Reyes E. Tutorial survival estimation for cyclooxygenase regression models with
time varying coecients using SAS and R. J stat softw. 2014;61(October):1-23.
doi:http://dx.doi.org/10.18637/jss.v061.c01
12. Badrey M, Abdel-Aziz H, Gomha S, et.al. Design and synthesis of imidazopyrazolopyridines as
novel selective cyclooxygenase 2 inhibitors. Molecules. 2015;20(8):15287-15303.
doi:10.3390/molecules200815287
13. Rouzer CA and Marnett LJ. Cyclooxygenases structural and functional insights. J Lipid Res.
2009;50(Supplement):29-34. doi:10.1194/jlr.R800042-JLR200
14. Visha MG. Selective cyclooxygenase 2 inhibitor. Int J Pharm Sci Invent. 2013;3(2):28-33.
http://www.ijpsi.org/Papers/Vol3(2)/E032028033.pdf.
15. Cesar B, Gurgel DV, Almeida TD, et.al. Selective cyclooxygenase 2 inhibitor meloxicam and
tooth supporting bone quality a histomorphometric study in rats. Brazilian Dent J.
2017;28(2):135-139.
doi:http://dx.doi.org/10.1590/0103-6440201701081 Selective
16. Mariana Orozco Solis, Celeste Pichardo Ramirez, Yazmin Garcia Avalos, et.al. Single dose of
diclofenac or meloxicam for control of pain facial swelling and trismus in oral surgery. Med Oral
Patol Oral Cir Bucal. 2016;21(1):127-134. doi:10.4317/medoral.20925
19
 International Journal of Research in Clinical Medicine and Pharmacy Practice. 2018;1(1) pg 13-20

17. Ahmad M, Murtaza G, Akhtar N, et.al. Bioequivalence study of two brands of meloxicam tablets
in healthy human Pakistani male subjects. Acta Pol Pharm Drug Res. 2011;68(1):115-119.
18. Chuang SY, Huey Yu Y, Herng Sheu W, et.al. Association of short term use of nonsteroidal anti
inflammatory drugs with stroke in patients with hypertension. Stroke Aha Journals.
2015;46(4):996-1003.
doi:10.1161/STROKEAHA.114.007932
19. Lanza FL, Chan FKL, Quigley EMM, et.al. Guidelines for prevention of NSAID related ulcer
complications. Am J Gastroenterol. 2009;104(3):728-738. doi:10.1038/ajg.2009.115
20. Hynninen V, Olkkola KT, Bertilsson L, et.al. Voriconazole increases while itraconazole decreases
plasma meloxicam concentrations. Antimicrob Agents Chemother. 2009;53(2):587-592.
doi:10.1128/AAC.00530-08
21. Meineke I and Turck D. Population pharmacokinetic analysis of meloxicam in rheumatoid
arthritis patients. Br J Clin Pharmacol. 2003;55(1):32-38. doi:10.1046/j.1365-
2125.2003.01753.x
22. Blain H, Boileau C, Lapicque F, et.al. Limitation of the in vitro whole blood assay for predicting
the cox selectivity of non selective anti inflammatory drugs in clinical use. Br J Clin Pharmacol.
2002;53(3):255-265.
doi:10.1046/j.0306-5251.2001.01533.x
23. Gorgel SN, Sefik E, Kose O, et.al. The effect of combined therapy with tamsulosin hydrochloride
and meloxicam in patients with benign prostatic hyperplasia symptoms and impact on nocturia
and sleep quality. Int Braz J Urol. 2013;39(5):657-662. doi:10.1590/S1677-
5538.IBJU.2013.05.07
24. Valat JP, Accardo S, Reginster JY, et.al. A comparison of the efficacy and tolerability of
meloxicam and diclofenac in the treatment of patients with osteoarthritis of the lumbar spine.
Inflamm Res. 2001;50(S1):30-34.
doi:10.1007/PL00000218
25. Thompson JP, Sharpe P, Kiani S, et.al. Effect of meloxicam on postoperative pain after
abdominal hysterectomy. Br J Anaesth. 2000;84(2):151-154.
doi:10.1093/oxfordjournals.bja.a013395
26. Kim JH, Park SH, Cho CS, et.al. Preventive efficacy and safety of rebamipide in nonsteroidal anti
inflammatory drug induced mucosal toxicity. Gut Liver. 2014;8(4):371-379.
doi:10.5009/gnl.2014.8.4.371
27. Macdonald TM, Mackenzie IS, Wei L, et.al. Methodology of a large prospective randomised open
blinded endpoint streamlined safety study of celecoxib versus traditional non steroidal anti
inflammatory drugs in patients with osteoarthritis or rheumatoid arthritis protocol of the
standard care. BMJ Open. 2013;3(1):22-95.
doi:10.1136/bmjopen-2012-002295
28. Batysheva TT, Otcheskaya OV, Khozova AA, et.al. Efficacy of the combination of arthrosan and
combilipen in patients with acute lower spinal pain. Neurosci Behav Physiol. 2013;43(2):240-
243.
doi:10.1007/s11055-013-9722-3
29. Frontlines T, Boano C, Lamarca MG, et.al. Endoscopic evaluation of non selective anti
inflammatory drugs induced gastric and duodenal ulcers during prophylaxis. J Gastroenterol
Hepatol Res. 2012;1(10):260-265.
doi:10.1177/0169796X1102700404
30. Zarif Najafi H, Oshagh M, Salehi P, et.al. Comparison of the effects of preemptive
acetaminophen ibuprofen and meloxicam on pain after separator placement a randomized
clinical trial. Prog Orthod A Springer Open J. 2015;16:34. doi:10.1186/s40510-015-0104-y
31. Zhang M, Yang Y, Zhao G, et.al. Effect of CYP2C9 mutant variants on meloxicam
pharmacokinetics in a healthy Chinese population. Genet Mol Res. 2014;13(1):831-837.
doi:10.4238/2014.February.13.1
32. Bykerk VP, Akhavan P, Hazlewood GS, et.al. Canadian rheumatology association
recommendations for pharmacological management of rheumatoid arthritis with traditional
and biologic disease modifying antirheumatic drugs. J Rheumatol. 2012;39(8):1559-1582.
doi:10.3899/jrheum.110207
33. Carvalho CDS, Andrade LEC, Keusseyan SP, et.al. Study of advanced rheumatoid arthritis. Rev
Bras Eng Biomed. 2014;30(1):54-63. doi:10.4322/rbeb.2014.004
34. Kumar V, Prakash J, Gupta V, et.al. Antioxidant enzymes in rheumatoid arthritis. J Arthritis.
2016;5(4):1-5. doi:http://dx.doi.org/10.4172/2167-7921.1000206 Research
35. Zeman MN and Scott PJ. Current imaging strategies in rheumatoid arthritis. Am J Nucl Med Mol
Imaging. 2012;2(2):174-220. http://www.pubmedcentral.nih.gov/articlerender.fcgi?
artid=3477730&tool=pmcentrez&rendertype=abstract.
36. Ruperto N, Nikishina I, Pachanov ED, et.al. A randomized double blind clinical trial of two doses
20
 International Journal of Research in Clinical Medicine and Pharmacy Practice. 2018;1(1) pg 13-20

of meloxicam compared with naproxen in children with juvenile idiopathic arthritis short and
long term efficacy and safety results. Arthritis Rheum. 2005;52(2):563-572.
doi:10.1002/art.20860
37. Symonds T, Hughes B, Liao S, et.al. Validation of the chinese western ontario and mcmaster
universities osteoarthritis index in patients from mainland china with osteoarthritis of the knee.
Arthritis Care Res. 2015;67(11):1553-1560. doi:10.1002/acr.22631
38. Girawan D, Abdurachman SA, Djumhana A, et.al. Comparison of endoscopic gastric mucosa
features after administration of piroxicam to meloxicam and their correlation with dyspepsia
symptoms in elderly patient with knee osteoarthritis. Acta Med Indones. 2004;36(4):202-206.
http://www.ncbi.nlm.nih.gov/pubmed/15673949.
39. Luo R, Liu G, Liu W, et.al. Efficacy of celecoxib meloxicam and paracetamol in elderly kashin
beck disease patients. Int Orthop. 2011;35(9):1409-1414. doi:10.1007/s00264-010-1062-0
40. Głuszko P and Stasiek M. Symptom modifying effects of oral avocado soybean unsaponifiables
in routine treatment of knee osteoarthritis in poland An open prospective observational study
of patients adherent to a 6 month treatment. Reumatologia. 2016;54(5):217-226.
doi:10.5114/reum.2016.63661
41. Macdonald TM, Ford I, Nuki G, et.al. Protocol of the febuxostat versus allopurinol streamlined
trial a large prospective randomised open blinded endpoint study comparing the
cardiovascular safety of allopurinol and febuxostat in the management of symptomatic
hyperuricaemia. BMJ Open. 2014;4(7):1-8. doi:10.1136/bmjopen-2014-005354
42. Goldstein JL, Miner PB, Schlesinger PK, et.al. Intragastric acid control in non steroidal anti
inflammatory drug users comparison of esomeprazole lansoprazole and pantoprazole. Aliment
Pharmacol Ther. 2006;23(8):1189-1196. doi:10.1111/j.1365-2036.2006.02867.x
43. Hanft G, Turck D, Scheuerer S, et.al. Meloxicam oral suspension a treatment alternative to solid
meloxicam formulations. Inflamm Res. 2001;50(S1):35-37. doi:10.1007/PL00000219
44. Van Kraaij DJW, Hovestad Witterland AHI, Metz M, et.al. A comparison of the effects of
nabumetone vs meloxicam on serum thromboxane B2 and platelet function in healthy
volunteers. Br J Clin Pharmacol. 2002;53(6):644-647. doi:10.1046/j.1365-2125.2002.01605.x
45. Prieto A, De Barrio M, Martin E, et.al. Tolerability to nabumetone and meloxicam in patients
with nonsteroidal anti inflammatory drug intolerance. J Allergy Clin Immunol. 2007;119(4):960-
964.
doi:10.1016/j.jaci.2006.12.616
46. Altman R, Hochberg M, Gibofsky A, et.al. Efficacy and safety of low dose solumatrix meloxicam
in the treatment of osteoarthritis pain a 12 week phase 3 study. Curr Med Res Opin.
2015;31(12):2331-2343.
doi:10.1185/03007995.2015.1112772
47. Cecile GV, Fautrel B, Hosseini K, et.al.Variability of the SF 6D determinants over time in early
arthritis results from the espoir cohort. Arthritis Rheum. 2012;64(10):36-37.
doi:http://dx.doi.org/10.1002/art.37735
48. Altman R, Luciardi H, Muntaner J, et.al. Efficacy assessment of meloxicam a preferential
cyclooxygenase 2 inhibitor in acute coronary syndromes without segment elevation the
nonsteroidal anti inflammatory drugs in unstable angina treatment pilot study. Circ Aha Journol.
2002;106(2):191-195.
doi:10.1161/01.CIR.0000021599.56755.A1
49. Rys P, Władysiuk M, Skrzekowska-Baran I, et.al. Review articles systematic reviews and meta
analyses which can be trusted. Pol Arch Med Wewnętrznej. 2009;119(3):148-156.
http://www.ncbi.nlm.nih.gov/pubmed/19514644.
50. Liberati A, Altman DG, Tetzlaff J, et.al. The PRISMA statement for reporting systematic reviews
and meta analyses of studies that evaluate health care interventions explanation and
elaboration. Plos Med. 2009;6(7):1000100. doi:10.1371/journal.pmed.1000100
51. Akhilesh Gupta and Swati Rawat. Pharmacoepidemiology of severe systemic infection and
need of netilmicin monotherapy or combination therapy. Research Journal of Pharmaceutical
Dosage Forms and Technology. 2017;9(3):101-108. doi: 10.5958/0975-4377.2017.00018.0
52. Ohtori S, Inoue G, Orita S, et.al. Efficacy of combination of meloxicam and pregabalin for pain
in knee osteoarthritis. Yonsei Med J. 2013;54(5):1253-1258. doi:10.3349/ymj.2013.54.5.1253
53. Chopra A, Saluja M, Venugopalan A, et.al. Effectiveness of chloroquine and inflammatory
cytokine response in patients with early persistent musculoskeletal pain and arthritis following
chikungunya virus infection. Arthritis Rheumatol. 2014;66(2):319-326. doi:10.1002/art.38221
54. Akhilesh Gupta and Swati Rawat. Simultaneous estimation of amoxicillin and potassium
clavulanate in injection formulation by dual wavelength spectroscopy. Drug Invention Today
2011; 3: 33-34.

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 International Journal of Research in Clinical Medicine and Pharmacy Practice. 2018;1(1) pg 13-20

55. Akhilesh Gupta and Swati Rawat. Simultaneous estimation of amoxicillin and potassium
clavulanate in injection formulation by simultaneous equation method. Journal of Pharmacy
Research 2011; 4: 1244-45.
56. Swati Rawat and Akhilesh Gupta. Spectrophotometric method for simultaneous estimation of
nimesulide and diclofenac sodium in pharmaceutical dosage form. Asian Journal of
Pharmaceutical Analysis 2011; 1:85-87.
57. Akhilesh Gupta and Swati Rawat. An analytical approach for the determination of amoxicillin
and potassium clavulanate in pharmaceutical dosage form: review. Drug Invention Today 2011;
3: 35-37.
58. Swati Rawat and Akhilesh Gupta. Development of novel HPTLC method for estimation of
Qurcetine in Ocimum sanctum. Asian Journal of Pharmaceutical Technology 2011; 1: 149-51.
59. Akhilesh Gupta and Swati Rawat. Clinical Research and Therapeutic Importance of Dietary
Supplement L- Carnitine: Review. Asian Journal of Pharmaceutical Research 2018; 8: 47-58.
60. Swati Rawat and Akhilesh Gupta. Clinical importance of aloevera: Review. Research Journal of
Topical and Cosmetic Science 2017; 8: 30-39.
61. Akhilesh Gupta. Systematic Approach to Novel Drug Delivery System. A & V Publication India.
Ist edition 2018, pp 58-64.
62. Akhilesh Gupta and Swati Rawat. Synthesis and cyclization of benzothiazole: Review. Journal of
Current Pharmaceutical Research 2010; 3: 13-23.
63. Akhilesh Gupta and Swati Rawat. Synthesis and antifungal study of novel fluorobenzothiazole
derivatives. International Journal of Chemical and Analytical Science 2010, 1: 224-28.
64. Akhilesh Gupta and Swati Rawat. Synthesis and antibacterial study of novel
fluorobenzothiazole derivatives. Journal of Pharmacy Research 2010; 3: 2615-19.
65. Akhilesh Gupta and Swati Rawat. Therapeutic importance of benzothiazole: Review. Asian
Journal of Research in Chemistry 2010; 3: 821-96.
66. Akhilesh Gupta and Swati Rawat. Plazomicin: A step toward next generation aminoglycosides.
Review. Asian Journal of Research in Pharmaceutical Science 2017; 7:173-180.
67. Akhilesh Gupta and Swati Rawat. Method development and photolytic degradation study of
doxofylline by RP-HPLC and LC-MS/MS. Journal of Pharmacy Research 2011; 4: 1248-50.
68. Akhilesh Gupta and Swati Rawat. Method development and alkali degradation study of
doxofylline by RP-HPLC and LC-MS/MS. Drug Invention Today 2011; 3: 30-32.
69. Akhilesh Gupta and Swati Rawat. Method development and hydrolytic degradation study of
doxofylline by RP-HPLC and LC-MS/MS. Asian Journal of Pharmaceutical Analysis. 2011; 1: 14-
18.
70. Akhilesh Gupta and Swati Rawat. An analytical approach of doxofylline: Review. Asian Journal
of Pharmaceutical Analysis 2011; 1: 67-70.

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