Physiologically based pharmacokinetic model for cefazolin in rabbits and its preliminary extrapolation to man

A. Tsuji, K. Nishide, H. Minami, E. Nakashima, T. Terasaki, T. Yamana

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

In the present study, the physiologically based pharmacokinetic model, which succeeded previously in predicting the pharmacokinetics of β-lactam antibiotics in rats was applied to cefazolin pharmacokinetics in rabbits and man. After iv bolus dosing in normal rabbits, the time courses of cefazolin concentration in plasma and various tissues (lung, heart, muscle, skin, bone, gut, liver, and kidney) were found to be very similar to those in rats. The values of physiological parameters (tissue plasma flows, tissue volumes, tissue/plasma albumin ratio) and biochemical parameters determined in this study (for nonlinear plasma protein binding, intrinsic renal clearance of active secretion and reabsorption) were incorporated into mass balance equations derived from the model. There was reasonable agreement between the model predictions and the observed data for cefazolin and inulin in rabbits. The model was also successful in the prediction of cefazolin disposition in rabbits with renal failure. Using available information reported for cefazolin in man, a preliminary extrapolation from the present model was attempted, and the overall predicted results after iv administration of 1 g cefazolin in man were compared with the serum and bone tissue data. The length of the effective antibacterial period for the drug is also discussed in terms of its predicted concentration unbound with proteins in various tissue interstitial fluids in man.

Original languageEnglish
Pages (from-to)729-739
Number of pages11
JournalDrug Metabolism and Disposition
Volume13
Issue number6
Publication statusPublished - 1985
Externally publishedYes

Fingerprint

Cefazolin
Pharmacokinetics
Extrapolation
Tissue
Rabbits
Rats
Bone
Kidney
Bone and Bones
Plasma flow
Lactams
Inulin
Extracellular Fluid
Protein Binding
Serum Albumin
Liver
Renal Insufficiency
Muscle
Blood Proteins
Myocardium

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Tsuji, A., Nishide, K., Minami, H., Nakashima, E., Terasaki, T., & Yamana, T. (1985). Physiologically based pharmacokinetic model for cefazolin in rabbits and its preliminary extrapolation to man. Drug Metabolism and Disposition, 13(6), 729-739.

Physiologically based pharmacokinetic model for cefazolin in rabbits and its preliminary extrapolation to man. / Tsuji, A.; Nishide, K.; Minami, H.; Nakashima, E.; Terasaki, T.; Yamana, T.

In: Drug Metabolism and Disposition, Vol. 13, No. 6, 1985, p. 729-739.

Research output: Contribution to journalArticle

Tsuji, A, Nishide, K, Minami, H, Nakashima, E, Terasaki, T & Yamana, T 1985, 'Physiologically based pharmacokinetic model for cefazolin in rabbits and its preliminary extrapolation to man', Drug Metabolism and Disposition, vol. 13, no. 6, pp. 729-739.
Tsuji, A. ; Nishide, K. ; Minami, H. ; Nakashima, E. ; Terasaki, T. ; Yamana, T. / Physiologically based pharmacokinetic model for cefazolin in rabbits and its preliminary extrapolation to man. In: Drug Metabolism and Disposition. 1985 ; Vol. 13, No. 6. pp. 729-739.
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