Vol.53 No.6 June 2005
Influence of malignancy on the pharmacokinetics of vancomycin hydrochloride in Japanese MRSA patients after dosage adjustment with the Bayesian method
1)Department of Pharmacy, Nishimino Kouse Hospital, 986 Oshikoshi, Yoro-cho, Yoro-gun, Gifu, Japan
2)Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa University
Abstract
We experienced a case in which serum vancomycin (VCM) concentration was fairly lower than the expected concentration from the usual dosage in the case of a normal renal function patient with methicillin-resistant Staphylococcus aureus (MRSA). The patient had lung cancer. Therefore, in this study, it was determined whether the presence of malignancy alters VCM pharmacokinetic parameters and dosage reuirements in Japanese cancer patients with normal renal function (serum creatinine of <0.6 mg/dL).
This study evaluates the influence of malignancy on the pharmacokinetics and dosage requirements of VCM in 25 patients with cancer (age 63.4±9.7 years, mean±S.D.) compared with 27 patients without cancer (age 69.3±14.5 years) using a two-compartment Bayesian pharmacokinetic program. After dosage adjustment, patients in the malignancy group required a VCM dosage regimen of 34.86±13.09 mg/kg/day to attain a mean trough serum VCM concentration of 10.96±4.07 μg/mL and a mean peak serum VCM concentration of 25.51±1.92 μg/mL. Patients without cancer in the control group required a mean VCM dosage regimen of 26.40±11.22 mg/kg/day to attain a mean trough serum VCM concentration of 10.53±3.01 μg/mL and a mean peak serum VCM concentration of 24.18±0.11 μg/mL. Comparative analysis of the pharmacokinetic data revealed an increase in VCM clearance (0.077±0.029 L/hr/kg) in the malignancy group as compared with that (0.056±0.018 L/hr/kg) in the control group. In addition, the values of the volume of distribution (1.29±0.41 L/kg) increased in the malignancy group as compared with those (1.05±0.34 L/kg) in the control group.
Analysis of the predictive performance of the Bayesian program indicated that the final sets of peak and trough serum VCM concentration were predicted with minimal bias and accurate precision in both study groups. This study showed that the presence of malignancy increased VCM clearance resulting in larger dosage requirements.
Key word
vancomycin, malignancy, pharmacokinetic parameter, Bayesian method
Received
October 15, 2004
Accepted
April 14, 2005
Jpn. J. Chemother. 53 (6): 357-363, 2005
