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Effect of Age and Renal Function on the Pharmacokinetics of Coadministered Cefoperazone and Sulbactam

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Summary

The single dose pharmacokinetics of cefoperazone 1g and sulbactam 0.5g, coadministered intravenously, were evaluated in 3 different age groups. Eight healthy young, 8 healthy middle-aged, and 8 healthy elderly adults were studied in an open design. The terminal half-life of cefoperazone (3.0 vs 2.3 hours) was 1.3 times greater in the elderly than in the young subjects and 2.5 times greater for sulbactam (1.8 vs 0.7 hours). Total sulbactam clearance was found to correlate better with age (r = 0.59) than was total cefoperazone clearance (r = 0.40). Volume of distribution, adjusted for bodyweight, remained constant with age. The relationship between creatinine clearance (CLcr) and age in this study is described as (CLcr = −1.37 age + 158.28; r = 0.72, p = 0.0001). Multivariate regression analysis of total body clearance versus age and creatinine clearance did not significantly improve the correlation for sulbactam (r = 0.62, p = 0.95) or cefoperazone (r = 0.44, p = 0.87). Sulbactam remained at or above the serum concentrations (8 mg/L) considered to provide optimal synergy with cefoperazone for 1.8, 2.2 and 3.3 hours postinfusion in the young, middle-aged and elderly subjects, respectively.

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Authors and Affiliations

  1. Department of Veterans Affairs West Los Angeles Medical Center, Pharmacy Services, Los Angeles, California, USA

    J. P. Rho (Director of Pharmacy)

  2. Department of Veterans Affairs West Los Angeles Medical Center, Geriatric Research, Education and Clinical Center, Los Angeles, California, USA

    S. Castle, K. Smith & D. C. Norman

  3. Department of Veterans Affairs West Los Angeles Medical Center, Medical Services, Los Angeles, California, USA

    S. Castle & D. C. Norman

  4. Department of Medicine, UCLA School of Medicine Los Angeles, California, USA

    S. Castle & D. C. Norman

  5. Department of Obstetrics and Gynecology, Southwestern School of Medicine, University of Southwestern Medical Center at Dallas, Dallas, Texas, USA

    R. E. Bawdon

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  1. J. P. Rho
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  2. S. Castle
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  3. K. Smith
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  4. R. E. Bawdon
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  5. D. C. Norman
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Rho, J.P., Castle, S., Smith, K. et al. Effect of Age and Renal Function on the Pharmacokinetics of Coadministered Cefoperazone and Sulbactam. Drug Invest. 6, 303–310 (1993). https://doi.org/10.1007/BF03259605

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