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J Pharm Pharmacol. 2019 Aug;71(8):1262-1270. doi: 10.1111/jphp.13105. Epub 2019 May 27.

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

Author information

1
Institute for Diagnostic and Interventional Radiology, Hannover Medical School, Hannover, Germany.
2
Nephrology Hannover Medical School, Hannover, Germany.
3
Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover, Hannover, Germany.
4
Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Wuppertal, Germany.
5
Medical Clinic V (Nephrology, Rheumatology, Blood Purification), Academic Teaching Hospital Braunschweig, Braunschweig, Germany.
6
Section on Experimental Radiology, University of Tuebingen, Tübingen, Germany.

Abstract

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.

KEYWORDS:

arterial spin labelling; diclofenac; functional magnetic resonance imaging; non-steroidal anti-inflammatory drug; renal perfusion

PMID:
31131893
DOI:
10.1111/jphp.13105

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