In vitro activity of BMY-28100 against common isolates from pediatric infections

The objective of this Phase I study was to evaluate the safety, tolerance, and pharmacokinetics of BMY-28100 in 36 male subjects after the administration of single oral doses of 250, 500, and 1,000 mg. The subjects were divided into groups of 12 per dose group. All subjects completed the study, and BMY-28100 was well tolerated at all doses. The maximum concentration of the drug in plasma ranged from 6.2 to 17.7 Ig/mL for the 250-and 1,000-mg doses, respectively, and the area under the curve increased in a dose-proportional manner. The elimination half-life and renal clearance averages were 1.2 h and 200 ml/min, respectively. The values for renal clearance suggest that BMY-28100 is excreted by glomerular filtration and tubular secretion. Mean concentrations of the drug in urine were highest during the first 4 h after the doses and ranged from 175 to 658 .g/ml following the 250-and 1,000-mg doses, respectively. The mean urinary recovery ranged from 57 to 70% of the dose. The results from this Phase I study indicate that BMY-28100 is well tolerated and exhibits linear pharmacokinetics.

mentioning

confidence: 99%

Phase I study of single-dose BMY-28100, a new oral cephalosporin

Barbhaiya

Gleason

Shyu

et al. 1990

“…Cefprozil is an oral cephalosporin with an antibacterial spectrum that includes important gram-positive and gramnegative pathogens usually associated with infections of the urinary and respiratory tracts (5,8,11,16). It is structurally similar to other cephalosporins in that it has a phenylglycine side chain.…”

mentioning

confidence: 99%

Phase I study of multiple-dose cefprozil and comparison with cefaclor

Barbhaiya

Shukla

Gleason

et al. 1990

The objectives of this study were to assess the safety and tolerance of cefprozil, to characterize the pharmacokinetics of cefprozil after adiinistration of multiple doses of the drug, and to compare these pharmacokinetic parameters with those obtained with cefaclor. The volunteers received 28 doses of 250, 500, or 1,000 mg of cefprozil or 500 mg of cefaclor every 8 h for 10 days. Serial blood samples and the total volume of urine voided by each individual were collected for pharmacokinetic evaluation on days 1, 5, and 10. Both cephalosporins were well tolerated after multiple oral dosing. The greater than that of cefaclor. The half-life of cefprozil was also twofold longer than that observed for cefaclor. Although the urinary recovery of cefaclor (75% of dose) was significantly higher than that of cefprozil (61% of dose), the concentrations of cefprozil in urine remained significantly higher than those of cefaclor from 2 to 8 h postdosing. If the therapeutic concept is maintained that levels of beta-lactam antibiotics in plasma should exceed the MIC for the offending organisms over a period that approximates the dosing interval, then cefprozil would appear to be suitable for twice-daily administration, whereas cefaclor should probably be administered three or even four times a day.

“…Its broad-spectrum antibacterial activity and stability to hydrolysis by many P-lactamase enzymes, in combination with a more prolonged half-life when compared to other oral cephalosporins, has elicited interest in its potential clinical benefits for the treatment of various infections. In vitro data suggest that cefprozil is more active than either cefaclor or cephalexin against Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis (4,5,7,10,13). The average half-life in blood of cefprozil is 1.2 h, in contrast to the serum half-life of cefaclor of 0.6 to 0.9 h (2).…”

mentioning

confidence: 78%

Comparative efficacy and safety of cefprozil (BMY-28100) and cefaclor in the treatment of acute group A beta-hemolytic streptococcal pharyngitis

Christenson

Swenson

Gooch

et al. 1991

Cefprozil (BMY-28100) is a semisynthetic cephalosporin with broad-spectrum antibacterial activity and prolonged serum elimination half-life allowing for once-a-day oral administration. In vitro, cefprozil demonstrates excellent activity against Staphylococcus aureus, Streptococcus pyogenes, Haemophilus influenzae, and Moraxella catarrhalis. Cefprozil (500 mg once daily) was compared to cefaclor (250 mg three times daily) in an open, randomized, comparative trial for the treatment of acute group A beta-hemolytic streptococcal pharyngitis. Ninety-four patients were enrolled in this study; 53 patients were evaluable for clinical and bacteriological response assessment. Seventy-eight patients were evaluable for safety assessment. Three patients (all in the cefprozil treatment group) required disenrollment because of side effects, mainly nausea. Clinical and bacteriological responses were comparable for both study drugs. Leukopenia and nausea, the most common side effects observed, were more common in the cefprozil-treated group. Cefprozil appears to be an appropriate alternative to cefaclor for the treatment of acute group A beta-hemolytic streptococcal pharyngitis. However, because of the small number of patients eligible for efficacy assessment, a large type II (beta) error was expected in our study, which may have resulted in a potential failure to detect a difference between both treatment groups. A larger study would be required to determine the proper role of cefprozil in the treatment of group A beta-hemolytic streptococcal infections.