The novel therapeutic implications of azlocillin's dose-dependent pharmacokinetics: contributing physiologic mechanisms and a prospective, cross-over designed trial.
Azlocillin is an important acylureido penicillin antibiotic for the management of complex gram-negative infections particularly those caused by Pseudomonas species. The current studies demonstrate that it manifests dose-dependent pharmacokinetics during the usual regimens of clinical dosing, that enterohepatic recirculation does not occur and that renal tubular secretion (maximum renal tubular secretory capacity 300 +/- 30 micrograms/min) and hepatic metabolism appear to be the dominant contributors to the dose-dependent nature of azlocillin. The possible therapeutic implications of azlocillin's dose dependency were evaluated by undertaking a six-day randomized, prospective, cross-over design study to evaluate the pharmacokinetic disposition of the drug during a 3-g q4h (typically used in adults) regimen versus a 5-g q8h regimen. By using the area under the serum-time concentration curve (AUC) as the major comparative parameter for these two regimens, the results demonstrate that both regimens provide approximately equal quantitative amounts of the drug systemically as a result of azlocillin's dose dependency. The AUC values, although not therapeutic end points, nonetheless correlate well with clinical response to antibiotic therapy. The 5-g q8h regimen was well tolerated. It is less disruptive for patients, requires half the number of intravenous administrations, 17% less drug, and is more cost effective than the 3-g q4h regimen.
Whelton
A
A
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Stout
R L
RL
Spilman
P S
PS
Delgado
F A
FA
Watson
A J
AJ
D000328:Adult; D001390:Azlocillin / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006207:Half-Life; D006801:Humans; D007408:Intestinal Absorption; D007676:Kidney Failure, Chronic / Q000503:physiopathology; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male
D001390:Azlocillin