Laboratory studies with BL-S 578 (Cefadroxil) a new broad-spectrum orally active cephalosporin

BL-S 578 (Cefadroxil) is a new orally active semisynthetic cephalosporin antibiotic with broad-spectrum antibacterial activity. The new compound was evaluated in vitro in comparison with cephalexin. Some properties studied such as, antibacterial activity, binding with serum proteins and stability in acid and neutral solution at 37° C for both cephalosporins were similar. In experimental infections of mice, the protective action of BL-S 578 was more effective than cephalexin against Staphylococcus aureus and Streptococcus pneumoniae. BL-S 578 was more resistant than cephalexin to the β-lactamases produced by Klebsiella pneumoniae and Escherichia coli

Pharmacokinetic properties of BL-S 786 (ceforanide) in human volunteers

BL-S 786 (Ceforanide) a new injectable semisynthetic cephalosporin, was administered to 10 human volunteers b.d. for 5 days i.m. and i.v. Serum levels were determined after the first, fifth and ninth dose. Urinary excretion was determined in all subjects after the first dose 0-3; 3-6; 6-9; 9-12; 12-24 hr after administration. For i.m. administration peak serum was achieved within 1 hr and detected up to 12 hr after the dose. For i.v. administration, peak serum was achieved within 0.5 hr and detected up to 12 hr after the dose. The serum concentration of BL-S 786, after repeated doses, did not demonstrate accumulation of the drug. About 27 to 36% of the administered dose was excreted unaltered in the urine, within 3 hr of a single parenteral dose. Urine concentration exceeded the minimal inhibitory concentration for 90-100% of the common Gram-negative urinary pathogens, 12 hr after the administered dose

Pharmacokinetics of Sulbactam/Ampicillin in Humans after Intravenous and Intramuscular Injection

We investigated the pharmacokinetic properties of sulbactam/ampicillin (S/A), after intravenous (0.5/1.0 and 1.0/2.0 g) and intramuscular (0.5/1.0 g) coadministration in 10 male subjects. After 1.0/2.0 g intravenous doses of S/A the half-lives (t( 1/2 β)) were 1.14 ± 0.14/1.09 ± 0.16 h. The values for plasma clearance (Cl(p)) were 198.83 ± 26.27/250.33 ± 39.28 ml/min and the renal clearance (Cl(r)) 173.50 ± 19.66/208.80 ± 26.43 ml/min. The post distributive volumes (V(β)) were 19.67 ± 3.24/23.56 ± 5.76 liters. Similar values were obtained after 0.5/1.0 g of S/A intravenous coinjection. After 0.5/1.0 g intramuscular coadministration the t( 1/2 β) values were 1.26 ± 0.18/1.20 ± 0.15 h. The values for Cl(p) were 208.00 ± 28.73/243.17 ± 33.24 ml/min, for Cl(r) 179.50 ± 20.26/202.67 ± 27.61 ml/min and for V(β) 22.27 ± 4.12/25.30 ± 4.87 liters. The renal clearance of sulbactam is comparable to that of ampicillin and both clearances are greater than the glomerular filtration rate, suggesting active renal tubular secretion of the two drugs. The large volumes of distribution, and the ratio K12/K21 = 0.5 show the extensive distribution of the two drugs into extracellular fluids. The very similar values of the pharmacokinetic parameters of sulbactam and ampicillin confirm that the kinetics of the two drugs closely resemble one another

Pharmacokinetics of Fluconazole in Normal Volunteers

The pharmacokinetic profile of fluconazole, after 100 mg i.v. infusion or oral administration of a single 50 mg or 150 mg dose, was investigated in 18 healthy volunteers. At a dose of 100 mg i.v., the half-life (t( 1/2 β)) was 29.73 ± 8.05h. The mean residence time in the plasma was 27.56 ± 5.98 h. The post-distributive volume V(β) = 52.16 ± 9.83 l, approximating that of total bodywater. Renal excretion accounted for 61.64 ± 8.80% of the drug elimination after 48 h, with renal clearance Cl(r) = 12.91 ± 2.83 ml/min. Plasma clearance (Cl(r)) was 21.03 ± 5.07 ml/min. At oral doses of 50 and 150 mg the distribution and elimination of fluconazole resembled that following i.v. infusion. The peak levels in plasma at 2.5 h were 0.93 ± 0.13 and 2.69 ± 0.43 μg/ml, respectively. The large distribution volume, the long half-life and mean residence times, combined with a rapid absorption after oral administration, suggest that fluconazole will be effective at a wide range of body sites

Pharmacokinetics of cefotetan in elderly subjects after intramuscular administration.

The pharmacokinetics of cefotetan were studied in 10 healthy male subjects 65-75 years of age with normal liver function and a creatinine clearance of greater than 80 ml/min after single 2 g intramuscular doses. The mean plasma level at 0.5 h was 52.50 +/- 9.16 micrograms/ml. Peak concentrations were 91.78 +/- 12.02 micrograms/ml at 3 h, declining to 10.33 +/- 2.18 micrograms/ml at 18 h, 4.0 +/- 1.12 micrograms/ml at 24 h after the start injection. The percentage of the dose recovered in urine (0 to 24 h) was 60.3%. Cefotetan plasma clearance showed a statistically significant correlation (r = 0.956, p less than 0.001) with measured creatinine clearance and the positive intercept ordinate confirmed a nonrenal clearance of the drug (biliary excretion). The normal age-related changes in cefotetan kinetics were relatively small and dosage adjustment was not necessary for normal elderly subjects requiring cefotetan