Effects of Nabumetone, A New Non-Steroidal Anti-Inflammatory Drug, on Urinary Prostaglandin Excretion in Man

Giannessi, Daniela; Lazzerini, Guido; Filipponi, P; Mannarelli, C.; Vaiani, G; Grossi, E.; Caterina, Raffaele De

doi:10.1006/phrs.1993.1126

“…Also, the present study confirms that indomethacin inhibits renin release [20,23,26,27]. Similar to results from other studies in humans [7][8][9], we found that nabumetone did not affect renal prostaglandin excretion at rest. Similar to results from other studies in humans [7][8][9], we found that nabumetone did not affect renal prostaglandin excretion at rest.…”

Section: Discussionsupporting

confidence: 93%

Non-steroidal anti-inflammatory drugs and renal response to exercise: a comparison of indomethacin and nabumetone

Olsen

¹

,

Jensen

²

,

Hansen

³

et al. 1999

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Nabumetone, a newer non-steroidal anti-inflammatory drug (NSAID) which preferentially blocks cyclo-oxygenase-2 activity, may be less nephrotoxic than indomethacin. This study tested whether nabumetone has effects different from those of indomethacin on exercise-induced changes in renal function and the renin-aldosterone system. In a randomized fashion, ten subjects were studied after indomethacin (100 mg), nabumetone (1 g) or no medication (control) administered orally at 22.00 hours on the day before each study day, and again at 8.00 hours upon arrival at the laboratory. Renal function was studied at baseline, during graded 20-min exercise sessions at 25%, 50% and 75% of the maximal oxygen uptake rate, and subsequently during two 1-h recovery periods. Heart rate, arterial blood pressure, cardiac output and plasma catecholamines at rest and during exercise were not altered by indomethacin or nabumetone. Indomethacin decreased urinary rates of excretion of 6-oxo-prostaglandin F(1alpha) (6-oxo-PGF(1alpha)) and thromboxane B(2) in all study periods. Nabumetone decreased 6-oxo-PGF(1alpha) excretion during and after exercise. Excretion rates for PGE(2) did not change. Neither indomethacin nor nabumetone changed baseline values or exercise-induced decreases in renal plasma flow or glomerular filtration rate. Indomethacin, but not nabumetone, decreased sodium excretion, urine flow rate and free water clearance. The renal response to exercise, however, remained unchanged. In contrast with nabumatone, indomethacin decreased the plasma renin concentration. Thus, during exercise, nabumetone may decrease the excretion of 6-oxo-PGF(1alpha) by inhibition of cyclo-oxygenase-1 or by inhibition of specific exercise-induced activation of cyclo-oxygenase-2, or both. None of the drugs changed the renal response to exercise. Inhibition by indomethacin of angiotensin II and thromboxane A(2) synthesis may, during exercise, counterbalance renal vasoconstriction caused by blockade of vasodilatory prostaglandins.

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“…In contrast with indomethacin, nabumetone preferentially inhibits cyclo-oxygenase-2 [6]. Similar to results from other studies in humans [7][8][9], we found that nabumetone did not affect renal prostaglandin excretion at rest. In addition, the present study demonstrates, for the first time, that acute administration of nabumetone in normal subjects has no effects on renal haemodynamics, sodium and water excretion, or plasma concentrations of renin and aldosterone.…”

Section: Discussionsupporting

confidence: 91%

“…The prodrug nabumetone, which is transformed in the liver into the active metabolite 6-methoxy-2-naphthylacetic acid, preferentially inhibits cyclo-oxygenase-2, whereas indomethacin is a strong inhibitor of cyclo-oxygenase-1 [5,6]. Previous studies have indicated that nabumetone does not decrease renal prostaglandin synthesis [7][8][9], and suggested that nabumetone may be less nephrotoxic than conventional NSAIDs in the treatment of elderly patients and patients with renal impairment [9,10].…”

Section: Introductionmentioning

confidence: 98%

Non-steroidal anti-inflammatory drugs and renal response to exercise: a comparison of indomethacin and nabumetone

Olsen¹,

JENSEN²,

HANSEN³

et al. 1999

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Nabumetone, a newer non-steroidal anti-inflammatory drug (NSAID) which preferentially blocks cyclo-oxygenase-2 activity, may be less nephrotoxic than indomethacin. This study tested whether nabumetone has effects different from those of indomethacin on exercise-induced changes in renal function and the renin-aldosterone system. In a randomized fashion, ten subjects were studied after indomethacin (100 mg), nabumetone (1 g) or no medication (control) administered orally at 22.00 hours on the day before each study day, and again at 8.00 hours upon arrival at the laboratory. Renal function was studied at baseline, during graded 20-min exercise sessions at 25%, 50% and 75% of the maximal oxygen uptake rate, and subsequently during two 1-h recovery periods. Heart rate, arterial blood pressure, cardiac output and plasma catecholamines at rest and during exercise were not altered by indomethacin or nabumetone. Indomethacin decreased urinary rates of excretion of 6-oxo-prostaglandin F(1alpha) (6-oxo-PGF(1alpha)) and thromboxane B(2) in all study periods. Nabumetone decreased 6-oxo-PGF(1alpha) excretion during and after exercise. Excretion rates for PGE(2) did not change. Neither indomethacin nor nabumetone changed baseline values or exercise-induced decreases in renal plasma flow or glomerular filtration rate. Indomethacin, but not nabumetone, decreased sodium excretion, urine flow rate and free water clearance. The renal response to exercise, however, remained unchanged. In contrast with nabumatone, indomethacin decreased the plasma renin concentration. Thus, during exercise, nabumetone may decrease the excretion of 6-oxo-PGF(1alpha) by inhibition of cyclo-oxygenase-1 or by inhibition of specific exercise-induced activation of cyclo-oxygenase-2, or both. None of the drugs changed the renal response to exercise. Inhibition by indomethacin of angiotensin II and thromboxane A(2) synthesis may, during exercise, counterbalance renal vasoconstriction caused by blockade of vasodilatory prostaglandins.

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“…This amount is within the recommended dose range to provide an optimal antiphlogistic effect (Insel 1996). In the current trial, the daily dose of ibuprofen was limited to 400 mg as this amount is regarded as sufficient to secure an anti‐inflammatory outcome (Giannessi et al 1993).…”

Section: Discussionmentioning

confidence: 99%

The effect of systemic administration of ibuprofen in the experimental gingivitis model

Sekino

¹

,

Ramberg

²

,

Lindhe

³

2005

J Clinic Periodontology

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Effects of Nabumetone, A New Non-Steroidal Anti-Inflammatory Drug, on Urinary Prostaglandin Excretion in Man

Cited by 9 publications

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Non-steroidal anti-inflammatory drugs and renal response to exercise: a comparison of indomethacin and nabumetone

Non-steroidal anti-inflammatory drugs and renal response to exercise: a comparison of indomethacin and nabumetone

Non-steroidal anti-inflammatory drugs and renal response to exercise: a comparison of indomethacin and nabumetone

The effect of systemic administration of ibuprofen in the experimental gingivitis model

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