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Ceftriaxone disposition in open-heart surgery patients
G L Jungbluth1, M T Pasko, T R Beam
1Department of Pharmaceutics, School of Pharmacy and Medicine, State University of New York, Buffalo 14260.
Antimicrobial Agents and Chemotherapy
|June 1, 1989
Summary
Cardiopulmonary bypass (CPB) significantly alters ceftriaxone pharmacokinetics, increasing free drug levels and half-life due to reduced albumin binding. This impacts drug efficacy and dosing during cardiac surgery.
Area of Science:
- Pharmacology
- Cardiovascular Surgery
Background:
- Cardiopulmonary bypass (CPB) involves hypothermia and heparinization, potentially affecting drug disposition.
- Understanding drug behavior during CPB is crucial for optimizing patient treatment.
Purpose of the Study:
- To evaluate the effects of CPB on the pharmacokinetic disposition of ceftriaxone.
- To investigate the influence of CPB-induced changes in albumin and free fatty acids on ceftriaxone binding.
Main Methods:
- Seven male patients undergoing CPB received a ceftriaxone bolus dose.
- Plasma and urine samples were collected pre-, during, and post-CPB for 96 hours.
- Measurements included total and free ceftriaxone, albumin, and creatinine; in vitro free fraction was determined by equilibrium dialysis.
Main Results:
- CPB significantly decreased plasma albumin levels and markedly increased ceftriaxone's in vitro free fraction.
- Reduced protein binding, attributed to low albumin and free fatty acids, increased ceftriaxone's volume of distribution and half-life.
- Intrinsic clearance decreased, while renal clearance due to filtration increased relative to creatinine clearance during CPB.
Conclusions:
- CPB significantly alters ceftriaxone disposition, leading to increased free drug concentrations and an extended half-life.
- Changes in albumin binding and potential interference from free fatty acids are key factors influencing ceftriaxone pharmacokinetics during CPB.
- These findings highlight the need for careful consideration of ceftriaxone dosing in patients undergoing CPB.