Pharmacokinetics and Protein Binding of Cefamandole and Its 1-Methyl-1 H-Tetrazole-5-Thiol Side Chain in Subjects with Normal and Impaired Renal Function

The 1-methyl-1 H-tetrazole-5-thiol (MTT) side chain present on several new cephalosporins may be an important factor in coagulopathy observed during therapy with these antibiotics. To determine the plasma kinetics and protein binding of the side chain and to test the hypothesis that renal failure al...

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Bibliographic Details
Published in:The Journal of infectious diseases 1986-06, Vol.153 (6), p.1069-1074
Main Authors: Aronoff, George R., Wolen, Robert L., Obermeyer, Boyd D., Black, Henry R.
Format: Article
Language:English
Subjects:
Adult
Antibacterial agents
Antibiotics
Antibiotics. Antiinfectious agents. Antiparasitic agents
Applied sciences
Azoles - metabolism
Biological and medical sciences
Bleeding
Blood plasma
Blood Proteins - metabolism
Cefamandole - analogs & derivatives
Cefamandole - metabolism
Cephalosporins
Dosage
Exact sciences and technology
Humans
Hypoprothrombinemias
Kidney failure
Kidney Failure, Chronic - metabolism
Male
Medical sciences
Metabolic Clearance Rate
Middle Aged
Original Articles
Other techniques and industries
Pharmacokinetics
Pharmacology. Drug treatments
Protein Binding
Renal function
Structure-Activity Relationship
Tetrazoles - metabolism
Volunteerism
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Summary:The 1-methyl-1 H-tetrazole-5-thiol (MTT) side chain present on several new cephalosporins may be an important factor in coagulopathy observed during therapy with these antibiotics. To determine the plasma kinetics and protein binding of the side chain and to test the hypothesis that renal failure alters these parameters, we gave six normal volunteers and six anuric patients a single iv dose of 15 mg of cefamandole/kg. Plasma concentrations of cefamandole and free MTT were measured by high-performance liquid chromatography 14 times during the 48-hr period after the dose was given. A compartment- independent pharmacokinetic analysis showed that MTT was rapidly removed from the plasma of normal subjects, but that peak concentrations of MTT were nearly three times greater and persisted for 48 hr in patients with renal failure. Further, renal failure caused a significant MTT protein-binding defect. Ifa relation exists between hypoprothrombinemia and plasma concentrations of MTTside chain, patients with reduced renal function may be at increased risk for this adverse effect.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/153.6.1069