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. 1973 Sep;4(3):366–371. doi: 10.1128/aac.4.3.366

Pharmacodynamics of Cefazolin in the Presence of Normal and Impaired Renal Function

Michael F Rein 1, Frederic B Westervelt 1, Merle A Sande 1
PMCID: PMC444558  PMID: 4758839

Abstract

The excretion of cefazolin, a new cephalosporin antibiotic, was studied in subjects with normal and impaired renal function. Twelve subjects with creatinine clearances ranging from 0 to 144 ml per min per 1.73 m2 were given a single 500-mg intramuscular dose of cefazolin. Serum and urine levels were determined at intervals by agar diffusion. Peak serum levels in normals ranged from 44 to 70 μg/ml and occurred 30 to 60 min after injection. The mean serum half-life in normals was 1.6 h, and this was prolonged from 20 to 40% by simultaneous administration of probenecid. The total elimination constant varied linearly with the creatinine clearance in patients with renal impairment. The serum half-life in anephric patients was about 42 h. The fractional clearance of the drug varied directly with the serum level. Peak urine levels ranged from 60 to over 2,000 μg/ml, and more than 90% of the dose was recovered in the urine of normals during the first 24 h. The data suggest that cefazolin is cleared primarily by the glomerulus, with tubular and biliary secretion playing a secondary role.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bennett J. V., Brodie J. L., Benner E. J., Kirby W. M. Simplified, accurate method for antibiotic assay of clinical specimens. Appl Microbiol. 1966 Mar;14(2):170–177. doi: 10.1128/am.14.2.170-177.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Gibaldi M., Schwartz M. A. Apparent effect of probenecid on the distribution of penicillins in man. Clin Pharmacol Ther. 1968 May-Jun;9(3):345–349. doi: 10.1002/cpt196893345. [DOI] [PubMed] [Google Scholar]
  3. Griffith R. S., Black H. R. Blood, urine and tissue concentrations of the cephalosporin antibiotics in normal subjects. Postgrad Med J. 1971 Feb;47(Suppl):32–40. [PubMed] [Google Scholar]
  4. Ishiyama S., Nakayama I., Iwamoto H., Iwai S., Okui M. Absorption, tissue concentration, and organ distribution of cefazolin. Antimicrob Agents Chemother (Bethesda) 1970;10:476–480. [PubMed] [Google Scholar]
  5. Kariyone K., Harada H., Kurita M., Takano T. Cefazolin, a new semisynthetic cephalosporin antibiotic. I. Synthesis and chemical properties of cefazolin. J Antibiot (Tokyo) 1970 Mar;23(3):131–136. doi: 10.7164/antibiotics.23.131. [DOI] [PubMed] [Google Scholar]
  6. Kirby W. M., De Maine J. B., Serrill W. S. Pharmacokinetics of the cephalosporins in healthy volunteers and uremic patients. Postgrad Med J. 1971 Feb;47(Suppl):41–46. [PubMed] [Google Scholar]
  7. Kozatani J., Okui M., Matsubara T., Nishida M. Cefazolin, a new semisynthetic cephalosporin antibiotic. VI. Excretion and metabolism of cefazolin- 14 C in rats after intramuscular administration. J Antibiot (Tokyo) 1972 Feb;25(2):86–93. [PubMed] [Google Scholar]
  8. Kozatani J., Okui M., Noda K., Ogino T., Noguchi H. Cefazolin, a new semisynthetic cephalosporin antibiotic. V. Distribution of cefazolin- 14 C in mice and rats after parenteral administration. Chem Pharm Bull (Tokyo) 1972 Jun;20(6):1105–1113. doi: 10.1248/cpb.20.1105. [DOI] [PubMed] [Google Scholar]
  9. LEE C. C., HERR E. B., Jr, ANDERSON R. C. Pharmacological and toxicological studies on cephalotin. Clin Med (Northfield) 1963 Jun;70:1123–1138. [PubMed] [Google Scholar]
  10. Nishida M., Matsubara T., Murakawa T., Mine Y., Yokota Y. Cefazolin, a new semisynthetic cephalosporin antibiotic. II. In vitro and in vivo antimicrobial activity. J Antibiot (Tokyo) 1970 Mar;23(3):137–148. doi: 10.7164/antibiotics.23.137. [DOI] [PubMed] [Google Scholar]
  11. Nishida M., Matsubara T., Murakawa T., Mine Y., Yokota Y., Goto S., Kuwahara S. Cefazolin, a new semisynthetic cephalosporin antibiotic. 3. Absorption, excretion and tissue distribution in parenteral administration. J Antibiot (Tokyo) 1970 Apr;23(4):184–194. [PubMed] [Google Scholar]
  12. Nishida M., Matsubara T., Murakawa T., Mine Y., Yokota Y., Kuwahara S., Goto S. In vitro and in vivo evaluation of cefazolin, a new cephalosporin C derivative. Antimicrob Agents Chemother (Bethesda) 1969;9:236–243. [PubMed] [Google Scholar]
  13. Regamey C., Humair L. Pharmacokinetics of cephalexin in renal insufficiency. Postgrad Med J. 1971 Feb;47(Suppl):69–78. [PubMed] [Google Scholar]
  14. Shibata K., Fujii M. Clinical studies of cefazolin in the surgical field. Antimicrob Agents Chemother (Bethesda) 1970;10:467–472. [PubMed] [Google Scholar]
  15. Tuano S. B., Brodie J. L., Kirby W. M. Cephaloridine versus cephalothin: relation of the kidney to blood level differences after parenteral administration. Antimicrob Agents Chemother (Bethesda) 1966;6:101–106. [PubMed] [Google Scholar]

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