Apparent biliary pseudolithiasis during ceftriaxone therapy.

Biliary pseudolithiasis has been reported in patients who received ceftriaxone therapy. To examine this phenomenon further, serial gallbladder sonograms were evaluated in 44 adult patients who received intravenous ceftriaxone at 2 g or a placebo daily for 14 days in a double-blind controlled study. Ultrasound examinations of gallbladders were performed on days 1 and 14 of therapy and 2 weeks posttherapy if abnormalities were observed on day 14. Eight patients were unevaluable because of abnormal base-line gallbladder sonograms. Thirty-six patients (ceftriaxone, n = 28; placebo, n = 8) demonstrated normal baseline gallbladder sonograms and were evaluated for the development of change. A total of 6 of 28 (21.4%) ceftriaxone-treated patients and 1 of 8 (12.5%) patients who received the placebo demonstrated abnormal gallbladder sonograms on day 14 (P = 0.491). Four of the six ceftriaxone-treated patients demonstrating abnormal sonograms were clinically asymptomatic, while two patients reported vomiting. The abnormal sonograms of gallbladders of patients treated with ceftriaxone returned to normal between 9 and 26 days posttherapy. These data suggest an association between ceftriaxone treatment and the development of gallbladder abnormalities on ultrasound examination which resolve spontaneously on discontinuation of ceftriaxone therapy.

Serum concentration and dose-response relationships for carprofen in rheumatoid arthritis.

Thirty-eight patients with active, definite, or classical rheumatoid arthritis were tested in a double-blind, 3-week-per-arm, multiple-crossover, randomized, block-design comparison of 100, 300, 600, and 800 mg/day carprofen given b.i.d. A linear dose-response relationship was demonstrated for six of nine efficacy measures (p less than 0.052). A plasma concentration to therapeutic response relationship was shown just before or 1 to 2 hours after a dose (p less than 0.05) for seven efficacy parameters for the patients with at least three serum carprofen concentrations. By nonparametric analysis, with the patients divided into three equal groups, the percent of responders rose from 38.1% to 50% to 59.1%. Sixty-nine percent of patients responded when carprofen concentrations were greater than 10 micrograms/ml, whereas only 9% responded when they were below 1.9 micrograms/ml. Although only seven patients had limiting side effects, there was a tendency toward a dose-toxicity relationship through 600 mg daily carprofen.

Effects of nonsteroidal, antiinflammatory drugs on gastrointestinal injury and prostanoid generation in healthy volunteers.

A new nonsteroidal, antiinflammatory drug, carprofen, was compared with indomethacin as to their effects on mucosal injury and prostanoid biosynthesis. A prospective, double-blind endoscopy study was performed in 40 healthy adults. After baseline normal endoscopy, 20 subjects were randomly assigned to either indomethacin (25 mg four times daily) or carprofen (150 mg twice daily) for eight days and re-endoscoped. Urinary and gastric mucosal prostaglandin generation, respectively, of PGE2 and PGF2 alpha, and PGE and 6-keto-PGF1 alpha was determined. Minor subjective symptoms occurred in six of 20 indomethacin (including four of eight with gastrointestinal injury) and in three of 20 carprofen subjects. Indomethacin and carprofen reduced gastric and urinary prostaglandin synthesis to a similar degree. Gastrointestinal injury was present in eight of 20 indomethacin and in none of 20 carprofen subjects. This study fails to establish a relationship between duodenal mucosal lesions and gastric prostanoid generation and confirms the lack of correlation between indomethacin-induced duodenal injury and subjective symptomatology. Carprofen appears to produce less objective damage in the upper gastrointestinal tract than indomethacin at comparable clinical doses.

Influence of food on bioavailability of amdinocillin pivoxil.

The bioavailability of amdinocillin was not altered when amdinocillin pivoxil was ingested 1 h before a standard breakfast, and it increased by 20% when amdinocillin pivoxil was ingested with or 1 h after a standard breakfast. Amdinocillin pivoxil would be convenient for patients since it may be taken with or without food.