Effects of naproxen and nabumetone on serum cholesterol levels in patients with osteoarthritis.

In a 12-week controlled clinical study of the effects of two nonsteroidal anti-inflammatory drug regimens on serum lipoproteins in patients with osteoarthritis, 54 patients were treated with naproxen, 500 mg twice daily, and 45 patients were treated with nabumetone, 1,000 mg once daily. In patients who received naproxen, the mean levels of total serum cholesterol decreased by 18.3 mg/dL (7.0%) from baseline to 12 weeks, high-density lipoprotein (HDL) cholesterol remained unchanged, and low-density lipoprotein (LDL) cholesterol decreased by 15.4 mg/dL (8.7%). In patients who received nabumetone, mean levels of total serum cholesterol increased 10.4 mg/dL (4.0%), HDL cholesterol remained unchanged, and LDL cholesterol increased 7.2 mg/dL (4.1%). Furthermore, serum triglyceride levels tended to increase in nabumetone-treated patients and decrease in naproxen-treated patients, with a statistically significant (P < 0.05) difference between treatments. The decreases in total cholesterol and LDL cholesterol levels in patients receiving naproxen were statistically significant (P < 0.01). These results confirm previous findings on naproxen's cholesterol-lowering effect.

A single-dose, double-blind comparison of naproxen sodium, acetaminophen, and placebo in postoperative dental pain.

The analgesic efficacy and duration of action of naproxen sodium 440 mg (n = 92), acetaminophen 1000 mg (n = 89), and placebo (n = 45) were compared in a single-dose, randomized, double-blind, 12-hour study of patients with at least moderate pain secondary to extraction of three or four third molars. Time to remedication, a measure of duration of analgesic effect, was significantly longer (P < 0.001) with naproxen sodium (median, 9.9 hours) than with either acetaminophen (median, 3.1 hours) or placebo (median, 2.0 hours). Naproxen sodium was also superior to acetaminophen for peak pain intensity difference (visual analog scale), summed pain intensity differences, total pain relief, peak pain relief, time to reduction of pain by 50%, and overall rating. The overall percentages of patients reporting adverse events, and the types of events reported, were comparable with the three treatments. Thus naproxen sodium demonstrated superior efficacy and similar tolerability to acetaminophen in this postoperative dental pain model.

A double-blind, randomized study of naproxen sodium, ibuprofen, and placebo in postoperative dental pain.

In a double-blind, parallel, placebo-controlled study, 203 patients with post-operative dental pain following the extraction of one or two bony impacted third molars were randomized to receive a single dose of naproxen sodium 220 mg, ibuprofen 200 mg or placebo. Pain intensity and pain relief were assessed at intervals for 12 hours postdose. Both active drugs demonstrated superior analgesic efficacy over placebo. Naproxen sodium and ibuprofen were comparable both in onset of analgesic action and in pain relief. From 1 to 12 hours postdose, naproxen sodium showed a trend for superior analgesic efficacy compared with ibuprofen; this trend reached statistical significance at the 12-hour time point. Both drugs were well-tolerated and effective analgesics for postoperative dental pain.

Pain relief after dental impaction surgery using ketorolac, hydrocodone plus acetaminophen, or placebo.

In a double-blind, placebo-controlled study, 207 patients with moderate pain after surgical removal of impacted third molars were randomly assigned to receive a single oral dose of 10 mg of ketorolac tromethamine, 10 mg of hydrocodone plus 1000 mg of acetaminophen, or placebo. Analgesic effect as assessed by summed pain intensity difference at 3 and 6 hours was significantly (P < or = 0.01) greater after ketorolac than after hydrocodone/acetaminophen. Total pain relief at 3 and 6 hours was significantly (P < 0.026) greater after ketorolac than after hydrocodone/acetaminophen or placebo. Patients taking hydrocodone/acetaminophen remedicated significantly (P = 0.027) sooner than those taking ketorolac. In this single-dose study, adverse events were reported more frequently by patients taking hydrocodone/acetaminophen than with ketorolac or placebo. It is concluded that, in this pain model, 10 mg of ketorolac affords better pain relief with fewer side effects than hydrocodone/acetaminophen.

Diuretic effect and metabolism of bumetanide in man.

Bumetanide (3-N-butylamino-4-phenoxy-5-sulfamyl-benzoic acid) is a sulfonamide congener with potent diuretic activity in man. Oral administration of 14C-bumetanide (2 mg, 22 71Ci) to 4 adult male volunteers was rapidly and almost completely absorbed (greater than 95%). Its average apparent volume of distribution was 25 L. Bumetanide induced a ceiling diuresis at 1 hr, with loss of Na+ and water for 4 to 5 hr. Loss of K+ was minimal. Bumetanide was quickly eliminated by metabolism and urinary excretion with a plasma half-life of 1.5 hr. The administered radioactivity was almost completely recovered (96%), 81% appearing in the urine and the remainder in the feces. In one subject with bilary T tube, 14.4% of the dose was excreted in the bile which suggested that the radioactivity of the feces came from the bile. Thin-layer chromatography analysis of pooled urine, bile, and fecal samples showed the elimination of bumetanide could be explained by excretion of unchanged drug and side chain oxidative metabolism and conjugation.