L-658,310, a new injectable cephalosporin. III. Experimental chemotherapeutics and pharmacokinetics in laboratory animals.
The therapeutic activity of L-658,310 was demonstrated in experimental bacteremias in normal, diabetic and neutropenic mice. Especially potent activity was shown against the usually difficult to control pathogens, Enterobacter cloacae and Pseudomonas aeruginosa, that were resistant to ceftazidime and/or gentamicin. Pharmacokinetic studies in mice showed a linear dose response in serum after the 20 and 50 mg/kg subcutaneous dose and urinary recoveries of administered dose of about 60% in 6 hours. Excretion was mainly by glomerular filtration. In a crossover design in rhesus monkeys, the pharmacokinetics of L-658,310 were similar to those of ceftazidime and suggest a moderately long half-life in serum of humans.
Gilfillan
E C
EC
Merck Sharp & Dohme Research Laboratories, Rahway, New Jersey 07065-0900.
Pelak
B A
BA
Weissberger
B A
BA
Abruzzo
G K
GK
Fromtling
R A
RA
Bland
J A
JA
Hadley
S K
SK
Gadebusch
H H
HH
D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy*; D002442:Ceftazidime / Q000493:pharmacokinetics / Q000627:therapeutic use; D002511:Cephalosporins / Q000493:pharmacokinetics / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D004352:Drug Resistance, Microbial; D004754:Enterobacter; D004756:Enterobacteriaceae Infections / Q000188:drug therapy; D005260:Female; D005839:Gentamicins / Q000627:therapeutic use; D006207:Half-Life; D054833:Isoindoles; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D009503:Neutropenia / Q000150:complications; D011552:Pseudomonas Infections / Q000150:complications / Q000188:drug therapy
D002511:Cephalosporins; D005839:Gentamicins; D054833:Isoindoles; C053266:BO 1236; D002442:Ceftazidime