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The Novel Therapeutic Implications of Azlocillin's Dose‐Dependent Pharmacokinetics: Contributing Physiologic Mechanisms and a Prospective, Cross‐Over Designed Trial
Author(s) -
Whelton Andrew,
Stout Robert L.,
Spilman Patricia S.,
Delgado Fernando A.,
Watson Alan J.
Publication year - 1987
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1987.tb03055.x
Subject(s) - azlocillin , pharmacokinetics , regimen , pharmacology , medicine , dosing , antibiotics , drug , chemistry , biology , pseudomonas aeruginosa , genetics , bacteria , piperacillin , biochemistry
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 μg/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.