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

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.

Prevention of hypophosphatemia during postoperative routine glucose administration.

The main study comprised 16 patients undergoing colon surgery. On the day of operation and the 3 following days 100 g of glucose was infused at the rate of 0.3 g/kg/h. Half the patients had 10 mmol of phosphorus added to each 1 000 ml 10% glucose solution. The investigation demonstrated that two different kinds of hypophosphatemia occur in the immediate postoperative period. A significant decrease in fasting plasma phosphate was found at the first, second and the third postoperative morning, most pronounced at the second day (1.20 +/- 0.05 to 0.78 +/- 0.07 mmol/l). A significant correlation between these changes and the corresponding 24-hour phosphorus balance was demonstrated (r = 0.61, p < 0.001). The falls in fasting phosphate could not be prevented by phosphorus addition because an amount of phosphorus corresponding to the amount added was excreted in excess in the urine. The plasma phosphate was decreased furthermore during and even 4 hours after the 5-hour glucose infusion (from 0.76 +/- 0.05 to 0.49 +/- 0.07 nmol/l at the end of the infusion at the second day). This hypophosphatemia was prevented by the phosphorus addition.--In average 3% of the infused sugar was lost in the urine. The solitary examples of higher losses (10-20%) were not followed by a higher urinary production. It is therefore concluded that 0.3 g glucose/kg/h is a suitable infusion rate in the immediate postoperative period.