Skin penetration and tissue permeation after topical administration of diclofenac

Hagen, Martina; Baker, Mark

doi:10.1080/03007995.2017.1352497

Cited by 105 publications

(99 citation statements)

References 109 publications

(194 reference statements)

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“…Topical application of diclofenac did not lead to therapeutic plasma concentrations, but measurable levels were verified in all study participants. It might well be that topical application correlates with higher local concentration in the tissue at the site of application . A strength of our study is that not only diclofenac plasma levels were measured but also target engagement indicated by reduction of thromboxane B2 during blood coagulation (serum generation) was analysed.…”

Section: Discussionmentioning

confidence: 99%

“…This was an observational study, and the sample size was determined based on previous pharmacological studies using CEUS or functional MRI for monitoring of renal perfusion as well as pharmacological studies on topical diclofenac application . In the mentioned work by Getzin et al ., a power calculation was performed for different scenarios with small pharmacological effects on renal perfusion.…”

Section: Methodsmentioning

confidence: 99%

“…Oral diclofenac is known to be absorbed faster and to lead to greater systemic bioavailability than topical application . Therefore, topical diclofenac administration is frequently discussed as an alternative for patients at risk of adverse drug events, since it might have less systemic side effects . Nonetheless, some preparations of topical diclofenac have been reported to reach measurable plasma concentrations after repeated application …”

Section: Introductionmentioning

confidence: 99%

“…[8,9] Therefore, topical diclofenac administration is frequently discussed as an alternative for patients at risk of adverse drug events, since it might have less systemic side effects. [8,10,11] Nonetheless, some preparations of topical diclofenac have been reported to reach measurable plasma concentrations after repeated application. [11][12][13] With contrast-enhanced ultrasound (CEUS), a discreet decrease in renal perfusion within 1 h after oral diclofenac application has been detected previously in healthy participants.…”

Section: Introductionmentioning

confidence: 99%

“…[8,10,11] Nonetheless, some preparations of topical diclofenac have been reported to reach measurable plasma concentrations after repeated application. [11][12][13] With contrast-enhanced ultrasound (CEUS), a discreet decrease in renal perfusion within 1 h after oral diclofenac application has been detected previously in healthy participants. [14] However, para-aminohippuric acid (PAH) clearance measurements did not reveal any changes in renal blood flow after oral application of diclofenac [15] or different NSAIDs such as etodolac or ibuprofen.…”

Section: Introductionmentioning

confidence: 99%

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Single-dose diclofenac in healthy volunteers can cause decrease in renal perfusion measured by functional magnetic resonance imaging

Hellms

Gueler

Gutberlet

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives We investigated changes of renal perfusion after topical and oral diclofenac administration in healthy volunteers using functional magnetic resonance imaging (MRI) with arterial spin labelling (ASL). Methods Twenty‐four healthy human participants (21–51 years) underwent 1.5T MRI before and 1 h after a single oral dose of diclofenac (50 mg). Twelve of 24 participants underwent an additional MRI examination following 3‐day topical diclofenac administration. For renal perfusion imaging, a flow‐sensitive alternating inversion‐recovery TrueFISP ASL sequence was applied. Plasma concentrations of diclofenac and serum concentrations of thromboxane were determined. Key findings After oral diclofenac application, large interindividual differences in plasma concentrations were observed (range <3–4604 nm). Topical diclofenac application did not result in relevant systemic diclofenac levels (range 5–75 nm). MRI showed a significant reduction of renal perfusion in individuals with diclofenac levels ≥225 nm (baseline: 347 ± 7 vs diclofenac: 323 ± 8 ml/min/100 g, P < 0.01); no significant differences were observed in participants with diclofenac levels <225 nm. Diclofenac levels correlated negatively with thromboxane B2 levels pointing towards target engagement. Conclusions Single‐dose diclofenac caused a decrease in renal perfusion in participants with diclofenac levels ≥225 nm. We demonstrated that even a single dose of diclofenac can impair renal perfusion, which could be detrimental in patients with underlying chronic kidney disease or acute kidney injury.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Single-dose diclofenac in healthy volunteers can cause decrease in renal perfusion measured by functional magnetic resonance imaging

Hellms

Gueler

Gutberlet

et al. 2019

Journal of Pharmacy and Pharmacology

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Synthesis, molecular dynamics simulation, and evaluation of biological activity of novel flurbiprofen and ibuprofen‐like compounds

Yıldız,

Osmaniye,

Saglik

et al. 2024

J of Molecular Recognition

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The frequent use of anti‐inflammatory drugs and the side effects of existing drugs keep the need for new compounds constant. For this purpose, flurbiprofen and ibuprofen‐like compounds, which are frequently used anti‐inflammatory compounds in this study, were synthesized and their structures were elucidated. Like ibuprofen and flurbiprofen, the compounds contain a residue of phenylacetic acid. On the other hand, it contains a secondary amine residue. Thus, it is planned to reduce the acidity, which is the biggest side effect of NSAI drugs, even a little bit. The estimated ADME parameters of the compounds were evaluated. Apart from internal use, local use of anti‐inflammatory compounds is also very important. For this reason, the skin permeability values of the compounds were also calculated. And it has been found to be compatible with reference drugs. The COX enzyme inhibitory effects of the obtained compounds were tested by in vitro experiments. Compound 2a showed significant activity against COX‐1 enzyme with an IC50 = 0.123 + 0.005 μM. The interaction of the compound with the enzyme active site was clarified by molecular dynamics studies.

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Topical nonsteroidal anti‐inflammatory drugs for management of osteoarthritis pain: A consensus recommendation

Lee¹,

Abbas

Cheah

et al. 2023

Journal Orthopaedic Research

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Osteoarthritis (OA) contributes to significant medical and socioeconomic burden in many populations. Its prevalence is expected to rise continuously owing to the combined effects of aging and increase in risk factors, including obesity, physical inactivity, and joint injuries. Pain is a hallmark presentation of OA. Topical nonsteroidal anti‐inflammatory drugs (NSAIDs) are recommended by many international guidelines as an early treatment option of the management of osteoarthritic pain. However, the use of topical NSAIDs remains low in Malaysia and appears not to be a preferred agent in managing OA pain by prescribers. There is also limited guidance from local medical bodies on the use of topical NSAIDs to manage OA pain. This consensus recommendation is intended to serve as a practical guide for healthcare practitioners on the use of topical NSAIDs in the management of OA pain. Eight statements and recommendations were finalized covering the areas of OA burden, topical NSAIDs formulations, safety and efficacy of topical NSAIDs, and patient education. Robust evidence is available to support the efficacy and safety of topical NSAIDs, with its benefits further strengthened by ease of use and access. Taking these into consideration, we recommend that healthcare practitioners advocate for the early use of topical NSAIDs over oral NSAIDs for mild‐to‐moderate OA pain, while engaging in a shared decision‐making process with patients for optimal clinical outcomes.

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Skin penetration and tissue permeation after topical administration of diclofenac

Cited by 105 publications

References 109 publications

Single-dose diclofenac in healthy volunteers can cause decrease in renal perfusion measured by functional magnetic resonance imaging

Single-dose diclofenac in healthy volunteers can cause decrease in renal perfusion measured by functional magnetic resonance imaging

Synthesis, molecular dynamics simulation, and evaluation of biological activity of novel flurbiprofen and ibuprofen‐like compounds

Topical nonsteroidal anti‐inflammatory drugs for management of osteoarthritis pain: A consensus recommendation

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