Vancomycin Pharmacokinetics in Patients with Advanced Cancer Near End of Life

European Journal of Drug Metabolism and Pharmacokinetics(2019)

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摘要
Background and Objective The effect of cancer cachexia on the pharmacokinetics of vancomycin remains unclear. We investigated whether the pharmacokinetics of vancomycin and the risk of kidney injury are altered with the development of cancer cachexia. Methods A retrospective analysis was conducted using therapeutic drug monitoring data obtained from 86 cancer patients who received vancomycin intravenously for infection. The patients were classified into four groups according to the stage of cachexia defined by international consensus—non-cachexia ( n = 26), pre-cachexia ( n = 10), cachexia ( n = 21) and refractory cachexia ( n = 29). Vancomycin pharmacokinetics were analyzed by a traditional one-compartment model and Bayesian method using plasma concentrations measured in these patients. Renal function and pharmacokinetic parameters were compared between the non-cachexia patients ( n = 26) and total cancer cachexia patients ( n = 60). Result No significant difference in estimated glomerular filtration rate was observed between the non-cachexia and the total cancer cachexia patients. In contrast, systemic clearance of vancomycin was significantly lower in the total cancer cachexia patients compared with the non-cachexia patients when analyzed by the traditional one-compartment model [median (range)—49.7 (9.8‒98.7) vs 70.2 (12.5‒211.8) mL/min, p < 0.01] and by the Bayesian method [45.6 (12.5–84.7) vs 63.3 (12.2–102.5) mL/min, p < 0.05]. None of the non-cachexia patients developed kidney injury, whereas 15% (9 of 60 patients) of the total cancer cachexia patients developed kidney injuries ( p = 0.052). Conclusions The present study revealed that cancer patients with cachexia may have reduced vancomycin clearance compared with those without cachexia. Cancer cachexia may be a risk factor of vancomycin-associated kidney injury, independent of renal function.
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