Objective. To preliminarily evaluate the safety and efficacy of different dose levels and dosing frequencies of recombinant human interleukin-1 receptor antagonist (rHuIL-1Ra) in the treatment of patients with rheumatoid arthritis (RA).Methods. One hundred seventy-five patients with active RA were enrolled in a randomized, double-blind trial of rHuIG1Ra administered by subcutaneous injection. There were 9 treatment groups in the trial. During the initial 3-week treatment phase, patients were treated with 20, 70, or 200 mg rHuIL-lRa, administered either once, 3 times, or 7 times per week, followed by a 4-week maintenance phase, during which all patients received the treatment-phase dose once per week. To maintain the blindness of the study, patients received daily injections of either rHuIL-1Ra or placebo on the days rHuIClRa was not administered.Results. Recombinant HuIL-1Ra was well tolerated. The most frequent adverse event was injection-site reactions, which were reported in 62% of patients and caused 8 patients (5%) to withdraw prematurely from the study. Five patients (3%) developed serious adverse reactions unrelated to dose or dosing frequency. Due to the lack of a placebo arm and to the multiple small treatment groups, a definitive statement regarding efficacy could not be made. However, by the end of the 3-week treatment phase, daily dosing appeared more effective than weekly dosing when assessed by the number of swollen joints, the investigator and patient asSupported by Synergen Inc.

Etanercept was slowly absorbed and slowly eliminated after subcutaneous administration. Dosing at the recommended rate of 25 mg twice weekly would be expected to result in concentrations of approximately 3 mg/L. Intersubject variability for apparent clearance in healthy volunteers was 64%.

Ten normal volunteers participated in a randomized, five-way crossover study to determine the effect of concurrent enoxacin and antacid or ranitidine administration on enoxacin absorption. The bioavailability of a single oral 400-mg enoxacin dose was significantly decreased, by 73 and 49%, when Maalox TC was administered 0.5 and 2 h before enoxacin, respectively. Enoxacin bioavailability was not significantly altered when the antacid was given 8 h before or 2 h after enoxacin administration. Ranitidine, administered intravenously 2 h before enoxacin, also significantly decreased enoxacin bioavailability, by 40%. The correlation between the proximity of antacid administration and the magnitude of the decrease in enoxacin bioavailability supports complexation as the mechanism of the antacid-enoxacin interaction. However, reduction of enoxacin bioavailability by ranitidine suggests that elevated gastric pH may also play a role in the antacid-enoxacin drug-drug interaction. Preheim et al., letter), and in normal volunteers, the bioavailability of ciprofloxacin was reduced by 90% when Maalox was coadministered (Hoffken et al., Int. Symp. New Quinolones).The present study was designed to determine the effect of concurrent antacid administration on the pharmacokinetics of the quinolone antibiotic enoxacin. The influence of the time of antacid administration relative to enoxacin administration on enoxacin bioavailability was investigated to determine whether enoxacin could be given to patients receiving intensive antacid therapy. In addition, the effect of ranitidine-induced gastric-acid suppression on enoxacin absorption was also studied. MATERIALS AND METHODSStudy design. Two males and eight females aged 20 to 40 years and weighing 54 to 78 kg participated in this nonblind, randomized, five-way crossover study. All subjects were in good health as determined by medical history, physical examination, electrocardiogram, and clinical laboratory tests. The protocol was approved by the Human Research Committee, and written informed consent was obtained from each subject. * Corresponding author.To facilitate sample collection, all enoxacin doses (400 mg) were administered in the morning. The five treatments, given at 1-week intervals, were (i) enoxacin alone, 30 min before breakfast; (ii) enoxacin administered 8 h after a bedtime antacid dose, 30 min before breakfast; (iii) enoxacin 30 min after antacid administration, 2 h before dinner; (iv) enoxacin administered 2 h after antacid administration, 0.5 h before dinner; and (v) enoxacin administered 2 h after a 50-mg intravenous ranitidine dose, 30 min before breakfast.As per clinical use, antacid doses were administered 1 and 3 h after meals and at bedtime during treatments 2, 3, and 4. Enoxacin is typically given twice daily, in the morning before breakfast and in the evening around dinner time. Therefore, enoxacin was administered 30 min before breakfast (treatment 2) and 0.5 and 2 h before dinner (treatments 3 and 4, respectively). Each enoxacin dose was administered with ...

The effect of gastric acidity on the oral absorption of the quinolone antibiotic enoxacin was evaluated in 12 healthy volunteers. In a randomized, crossover design, single 400 mg oral enoxacin doses were administered on four occasions: alone, after 50 mg intravenous ranitidine, after 2 micrograms/kg subcutaneous pentagastrin, and after combined ranitidine and pentagastrin treatment. Gastric pH was monitored by radiotelemetry capsule for 4 hours after enoxacin administration. Ranitidine pretreatment reduced enoxacin oral bioavailability by an average of 26%. This effect was abolished when pentagastrin was used to maintain low gastric pH. Thus the ranitidine-induced decrease in enoxacin oral bioavailability probably results from a decrease in gastric acidity rather than from an interaction with ranitidine itself.

There was a trend toward a slight improvement in neutrophil engraftment post-ABMT with the PIXY321 administered by an SC route compared with GM-CSF administered by an IV route. However, no differences could be identified between the two agents with respect to the time to platelet transfusion independence. Patient, regimen, and graft characteristics were most predictive of the engraftment tempo.