Hepatic safety of two analgesics used over the counter: ibuprofen and aspirin.

We evaluated the potential hepatic toxicity of ibuprofen, aspirin, and oxaprozin in 1468 patients with rheumatoid arthritis and osteoarthritis by slightly modifying an algorithm that was developed to evaluate the drug relatedness of renal toxicity associated with therapeutic doses of these agents in the same population. Ibuprofen proved to be the safest of these nonsteroidal antiinflammatory drugs; it was associated with no AST elevation that was considered probably drug related as determined by application of the algorithm to laboratory values and information from case report forms. The frequency of probably drug-related AST elevations was highest (5%) with aspirin; with oxaprozin, an investigational nonsteroidal antiinflammatory drug, the incidence (3%) fell between that for the other two agents. Thus our findings on the hepatic safety of ibuprofen are consistent with those in the medical literature.

A double-blind comparison of orally administered ciramadol and codeine for relief of postoperative pain.

Ciramadol, a new analgesic with mixed narcotic agonist-antagonist actions, was compared with codeine and placebo in a double-blind study in 343 patients with postoperative pain. The patients received a single oral dose of either 30 or 60 mg of ciramadol, 60 mg of codeine, or placebo. As indicated by three efficacy measures (verbal and visual analog pain scores and pain relief scores), the three active treatments were superior to placebo in relieving pain, and 30 and 60 mg of ciramadol generally were equivalent and superior, respectively, to 60 mg of codeine. The group who took 60 mg of ciramadol had a significantly (P less than .05) lower cumulative remedication frequency than that for the other three groups and the highest proportion of satisfactory evaluations by patients and physicians. There was no statistically significant difference in the incidence of side effects (4% to 11%) among the treatment groups. Demonstrated safety and efficacy suggest a role for ciramadol in the treatment of postoperative pain.

Lower esophageal sphincter response to oral administration of cimetidine in normal subjects.

Anithistamines that specifically block the gastric and secretory action of histamine have recently been developed. One of these H2-receptor blockers, metiamide, has been found to increase lower esophageal sphincter (LES) pressure in the opossum. Because of reported agranulocytosis with metiamide, another H2-receptor blocking agent, cimetidine, was developed. To determine its effect on LES pressure, 8 normal volunteers received placebo or oral doses of cimetidine (50, 100, 200, and 400 mg) in a random, blinded manner. Indicative of adequate absorption, significant serum levels were achieved with all doses of cimetidine (50 mg = 0.17 mug per ml; 100 mg = 0.33 mug per ml; 200 mg = 0.76 mug per ml; and 400 mg = 1.61 mug per ml). Although these serum levels have been found to produce marked inhibition of gastric acid secretion, no discernible effect was found on LES pressure when compared to placebo. Thus cimetidine does not increase LES pressure. It does not decrease sphincter pressure either and is therefore not contraindicated in patients with reflux esophagitis.

The metabolic disposition of 14C-ciramadol in humans.

Twelve subjects received single 15 mg oral doses of 14C-ciramadol. Excretion of the dose occurred almost entirely by the renal route (93.5 +/- 11.7 (S.D.)% of the dose), and only 0.7 +/- 0.6% of the dose was recovered in faeces indicating that absorption was essentially complete. More than 90% of the amount recovered in urine was excreted within 24 h after dosing. Unchanged drug accounted for 43.9 +/- 6.5% of the dose, while a phenolic glucuronide conjugate was the only major urinary metabolite accounting for a further 37.9 +/- 7.8%. A second glucuronide that was conjugated with the alicyclic ring was also identified but constituted only 2.3 +/- 0.6% of the dose. Concentrations of radioactivity in plasma reached a peak at 2 h after dosing and declined with a terminal disposition half life of 4.9 h. Only ciramadol and the aryl-O-glucuronide were detected in substantial amounts in plasma. Renal clearance of ciramadol amounted to 298 +/- 54 ml/min suggesting tubular secretion in addition to glomerular filtration.

Lower esophageal sphincter and gastric acid response to intravenous infusions of synthetic human gastrin I heptadecapeptide.

Human gastrin I heptadecapeptide was administered by constant intravenous infusion to 7 adult male volunteers without gastrointestinal disease, and serum gastrin concentrations and responses of the lower esophageal sphincter (LES) pressure and gastric acid output were measured and compared. Significant responses in LES pressure were found at gastrin infusion rates which produced submaximal gastric acid output. These LES pressure responses were quantitatively smaller than those occurring concomitantly with similar total immunoreactive gastrin levels evoked by administration of a protein meal in the same subjects. These observations suggest that, although increases in serum gastrin concentrations may contribute to increases in LES pressure seen under physiological conditions after feeding, the increase in LES pressure produced by feeding cannot be explained exclusively on the basis of endogenous gastrin release.