The pharmacokinetics and tissue penetration of ceftazidime and cefamandole in healthy volunteers.
Eight healthy male volunteers received either 1 g of ceftazidime or cefamandole as an intravenous bolus injection. Serial blood samples were taken over the following 8 h. Urine samples were collected over 24 h. Tissue fluid levels of the antibiotics were studied using a cantharides blister technique. Both drugs achieved high serum levels after intravenous injection (ceftazidime 83.3 mg/l, cefamandole 77.7 mg/l at 0.25 h). The serum half-lives were ceftazidime 1.8 h (S.D. 0.22), cefamandole 0.8 h (S.D. 0.07). The mean apparent volume of distribution of ceftazidime was greater than cefamandole (13.6 l compared with 9.8 l, respectively). The total clearance of ceftazidime was 111 ml/min (S.D. 16.6) compared to 216 ml/min (S.D. 30.1) for cefamandole. The maximum concentration of each drug in blister fluid was greater after ceftazidime (44.7 mg/l) than cefamandole (20.2 mg/l). The terminal half-life of ceftazidime in blister fluid (2.1 h) was similar to that in serum but the blister fluid halflife of cefamandole (1.22 h) was slightly prolonged compared with that in serum. suggested that ceftazidime attains levels in this tissue fluid model after a 1 g intravenous dose which might be sufficient to treat infections caused by Staphylococcus aureus, Pseudomonas aeruginosa as well as the common Gram-negatives.
Wise
E R
ER
Department of Microbiology, Dudley Road Hospital, Birmingham, England.
Armstrong
G C
GC
Brown
R M
RM
Andrews
J M
JM
D000287:Administration, Topical; D000328:Adult; D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001412:Bacillus subtilis / Q000187:drug effects; D001681:Biological Assay; D002435:Cefamandole / Q000493:pharmacokinetics*; D002442:Ceftazidime / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D012867:Skin / Q000378:metabolism; D014018:Tissue Distribution; D055815:Young Adult
D000900:Anti-Bacterial Agents; D002435:Cefamandole; D002442:Ceftazidime