Prolonged naproxen joint residence time after intra-articular injection of lipophilic solutions comprising a naproxen glycolamide ester prodrug in the rat

Thing, Mette; Lü, Yi; Ågårdh, Li; Larsen, Claus; Østergaard, Jesper; He, Wei; Wu, Wei; Larsen, Frank; Larsen, Susan Weng

doi:10.1016/j.ijpharm.2013.04.056

Cited by 9 publications

(6 citation statements)

References 42 publications

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“…However, surprisingly, when traditional formulations of NSAIDs are injected into synovial joints, the systemic exposure is very similar to that after IM or IV doses (Table 1). Although the majority of these PK studies were performed in rats, the relative bioavailability of IA NSAIDs compared to IM or IV doses was similar in all animal species regardless of NSAID tested (range 0.65–1.36) 12,28–31 . In humans, the bioavailability of indomethacin IA compared to IV was 0.78, demonstrating significant systemic exposure which is consistent with the rat PK experiments 32 .…”

Section: Resultssupporting

confidence: 63%

Pharmacokinetics, safety and efficacy of intra‐articular non‐steroidal anti‐inflammatory drug injections for the treatment of osteoarthritis: A narrative review

Selig

Kress

Horton

et al. 2022

Clinical Pharmacy Therapeu

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What is known and Objective Osteoarthritis (OA) is a common cause of joint disease and activity limitation in adults. Common therapies to treat OA‐related pain are oral and topical non‐steroidal anti‐inflammatory drugs (NSAIDs) and intra‐articular (IA) corticosteroids. However, prolonged courses of oral NSAIDs are associated with systemic adverse effects and repeat IA corticosteroid injections may cause cartilage degeneration. IA NSAIDs may be an alternative therapy possibly minimizing systemic side effects while maintaining efficacy. Therefore, we sought to summarize the pharmacokinetics, safety and efficacy of IA NSAIDs to help providers make a more informed decision on the use of IA NSAIDs. Methods We searched the National Library of Medicine Database with terms “intraarticular and nsaid”, yielding 1032 results. Only traditional formulations of NSAIDs were considered for inclusion. Animal studies were included if animals were healthy or if the method of arthritis induction was a reasonable model of osteoarthritis. Human studies were included if humans were healthy or if the primary disease studied was osteoarthritis of a large joint. Of 1032 results, 31 research articles met the inclusion criteria and were summarized in this review. Results and Discussion We found that single doses of IA NSAIDs provided far less total systemic and synovial exposure compared to a one week course of oral NSAIDs, but maximum concentrations to the synovium with IA administration were much higher. IA NSAIDs had an excellent safety profile in small animals, large animals and humans, although these injections were associated with non‐specific cartilage inflammation in healthy animals. In animal models, IA NSAIDs had similar efficacy to PO NSAIDs in treating OA‐related pain. In humans, IA NSAIDs had similar efficacy to PO NSAIDS and IA corticosteroids in treating OA‐related pain; however, many trials did not have a placebo control and outcome measures were heterogeneous. What is new and Conclusion Overall, single doses of IA NSAIDs appear safe and efficacious across animals and humans. The optimal use of IA NSAIDs is still to be determined and further research is needed. However IA NSAIDs may be an additional beneficial therapy to treat OA‐related pain. Potential uses may be to augment IA corticosteroids injections, to interrupt multiple IA corticosteroid injections or as an alternative in patients that are high risk for corticosteroid‐related adverse events.

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Section: Resultssupporting

confidence: 63%

Pharmacokinetics, safety and efficacy of intra‐articular non‐steroidal anti‐inflammatory drug injections for the treatment of osteoarthritis: A narrative review

Selig

Kress

Horton

et al. 2022

Clinical Pharmacy Therapeu

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“…Quite a lot of different naproxen prodrugs were synthesized and reported in the literature [5,6,[8][9][10][11][12][13][14][15]. However, the naproxen prodrug understudy here (referred to here after as pro-NP, Figure 2) contains and will release glycine in vivo which is not only safe but useful as a nutrient for the body.…”

Section: Introductionmentioning

confidence: 99%

“…Stability-indicating methods were described in the literature to study the chemical hydrolysis of naproxen prodrugs [12,13,15,[17][18][19]. Most of them employed HPLC with UV detection and C 18 columns for its simplicity the same as in the method below.…”

Section: Introductionmentioning

confidence: 99%

A Stability-Indicating RP-HPLC-UV Method for Determination and Chemical Hydrolysis Study of a Novel Naproxen Prodrug

Hamid

Elsaman

2017

Journal of Chemistry

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A new naproxen amide prodrug was synthesized and spectrally characterized and a simple, precise, and accurate stabilityindicating RP-HPLC method was developed and validated for determination and chemical hydrolysis study of the prodrug. Forced degradation studies were conducted as per the International Conference on Harmonization (ICH) guidelines to establish the stability-indicating power of the method. Separations were performed on a C 18 column (150 × 4.6 mm i.d., 5 m p.s.). The mobile phase consisted of acetonitrile and phosphate buffer pH 4.0 in the ratio 60 : 40. The flow rate and injection volume were 1.0 mL/min and 15 L, respectively. The peaks were monitored at 272 nm. The average retention time is 5.136 min. The linearity of the method was investigated in the range of 10-50 g/mL and 2 was found to be larger than 0.9987. The LOD and LOQ were found to be 1.853 and 5.615 g/mL, respectively. Results indicated that the degradants are well resolved and separated from the prodrug. Hydrolysis kinetics studies were carried out in buffer solutions (pH 1.2, 5.5 and 7.4) to establish the fate of the prodrug. The half-lives in the respective buffers were 23.5, 262, and 334 hours indicating sufficient stability to attain the goal of oral delivery.

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“…Glycolamide esters play the important role in modern biochemistry, medicinal chemistry, molecular biology, organic chemistry, and pharmacology. [9][10][11][12][13][14][15] On the other hands, promotion the overall lipophilicity of the molecule be able to promote membrane permeability and oral absorption. 13 With respect to prodrugs of a higher lipophilicity derived from bioactive compounds with carboxylic functions, glycolamide ester formation represents a well-known approach.…”

Section: Introductionmentioning

confidence: 99%

“…13 With respect to prodrugs of a higher lipophilicity derived from bioactive compounds with carboxylic functions, glycolamide ester formation represents a well-known approach. 11,13 Therefore, glycolamide esters often were reported as the potentially useful protecting groups of was completed (monitored by TLC), the co-solvent THF was added in the resulting solution. Sequentially, the key step of decarbonylation reaction was examined at the different reaction temperature and time.…”

Section: Introductionmentioning

confidence: 99%

Vilsmeier reagent initialed sequential one-pot multicomponent synthesis of N,O-disubstituted glycolamides as dipeptidyl peptidase 4 inhibitors

Yen

Tsai

et al. 2015

Tetrahedron

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Prolonged naproxen joint residence time after intra-articular injection of lipophilic solutions comprising a naproxen glycolamide ester prodrug in the rat

Cited by 9 publications

References 42 publications

Pharmacokinetics, safety and efficacy of intra‐articular non‐steroidal anti‐inflammatory drug injections for the treatment of osteoarthritis: A narrative review

Pharmacokinetics, safety and efficacy of intra‐articular non‐steroidal anti‐inflammatory drug injections for the treatment of osteoarthritis: A narrative review

A Stability-Indicating RP-HPLC-UV Method for Determination and Chemical Hydrolysis Study of a Novel Naproxen Prodrug

Vilsmeier reagent initialed sequential one-pot multicomponent synthesis of N,O-disubstituted glycolamides as dipeptidyl peptidase 4 inhibitors

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