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GASTRODUODENAL TOLERABILITY OF NIMESULIDE AND DICLOFENAC IN PATIENTS WITH OSTEOARTHRITIS

This 1-month, randomized, double-masked, parallel-group study was conducted to compare nimesulide (100 mg twice daily) with diclofenac (50 mg three times daily) with respect to gastroduodenal tolerability and efficacy in patients with osteoarthritis. Results of gastroduodenal endoscopy in 83 patients (42 receiving nimesulide, 41 receiving diclofenac) revealed that, after 30 days, 4 patients (1 nimesulide, 3 diclofenac) had developed ulcers and 6 patients (4 nimesulide, 2 diclofenac) had developed erosions; however, differences between the treatment groups were not statistically significant. Both study drugs were well tolerated. Ten patients (5 in each group) withdrew from the study prematurely because of adverse events. Efficacy was assessed by measuring pain on visual analogue scales, using the functional index of Lequesne, and by scoring spontaneous pain, pain on passive movement, and functional impairment. Nocturnal pain was also checked. All efficacy variables showed a significant improvement during the study, and no statistically significant differences were observed between the treatment groups.

Sources of glucose production in cirrhosis by 2H2O ingestion and 2H NMR analysis of plasma glucose

Plasma glucose 2H enrichment was quantified by 2H NMR in patients with cirrhosis (n=6) and healthy subjects (n=5) fasted for 16 h and given 2H(2)O to approximately 0.5% body water. The percent contribution of glycogenolysis and gluconeogenesis to glucose production (GP) was estimated from the relative enrichments of hydrogen 5 and hydrogen 2 of plasma glucose. Fasting plasma glucose levels were normal in both groups (87+/-7 and 87+/-24 mg/dl for healthy and cirrhotic subjects, respectively). The percent contribution of glycogen to GP was smaller in cirrhotics than controls (22+/-7% versus 46+/-4%, P<0.001), while the contribution from gluconeogenesis was larger (78+/-7% versus 54+/-4%, P<0.001). In all subjects, glucose 6R and 6S hydrogens had similar enrichments, consistent with extensive exchange of 2H between body water and the hydrogens of gluconeogenic oxaloacetate (OAA). The difference in 2H-enrichment between hydrogen 5 and hydrogen 6S was significantly larger in cirrhotics, suggesting that the fractional contribution of glycerol to the glyceraldehyde-3-phosphate (G3P)-moiety of plasma glucose was higher compared to controls (19+/-6% versus 7+/-6%, P<0.01). In all subjects, hydrogens 4 and 5 of glucose had identical enrichments while hydrogen 3 enrichments were systematically lower. This reflects incomplete exchange between the hydrogen of water and that of 1-R-dihydroxyacetone phosphate (DHAP) or incomplete exchange of DHAP and G3P pools via triose phosphate isomerase.

Efficacy of a single daily dose of a nonsteroidal anti-inflammatory drug with an intermediate plasma half-life : a double-blind, comparative trial of acemetacin and piroxicam

Abstract It has been proposed that the duration of the analgesic and anti-inflammatory effects of nonsteroidal anti-inflammatory drugs (NSAIDs) is longer than that expected from the plasma half-life values, with the possible exception of the salicylates. To determine the veracity of this statement, we conducted a double-blind clinical trial to compare piroxicam, an NSAID with a long half-life (about 40 hours) and acemetacin, an NSAID with an intermediate half-life (about 6 hours). Fifty-six patients of both sexes with a mean age of 54 years and with a clinical and radiologic diagnosis of osteoarthritis of the hip or the knee were enrolled. The initial treatment regimen consisted of a single daily capsule of either piroxicam 20 mg or acemetacin 90 mg to be taken at breakfast. The patients were instructed to take a second capsule at dinner whenever the single dose was found to be insufficient. Both drugs were shown to have substantial analgesic and anti-inflammatory activity and were equally effective. Ten (17.9% of the total study population) patients took more than one capsule a day. All of these patients had severe symptoms at the beginning of the trial, but eight patients required two capsules for only a brief period of 2 to 5 days. Thus only two patients (3.6% of the study population) required a regular twice-daily regimen. Acemetacin appeared to be better tolerated than piroxicam. Our results confirm that the duration of the clinical effects of NSAIDs cannot be predicted from their half-lives only.