아미노글라이코사이드계 항생제 투여용법을 1일 1회로 변경시 나타나는 약동학적 변수의 변화

Abstract

Aminoglycoside antibiotics are the representative drugs that require therapeutic drug monitoring (TDM). Recently the application of once-daily aminoglycoside dosing (ODD) is being extended as many studies suggested that ODD is as effective as traditional dosing (TD) and is not more toxic than TD. One of the ODD's merits is unlike TD there is no need for TDM, but ODD has been challenged by some studies suggesting the TDM is the most effective way to aminoglycoside dosing and by other studies insisting the utilization of nomogram based on 1~2 times measured actual blood drug level. ODD was not widely applied for aminoglycoside antibiotics in Seoul National University Hospital (SNUH). But in the case that aminoglycoside dosing regimen was changed from TD to ODD, we occasionally observed variation of pharmacokinetic parameters in their TDMs. So, this study was aimed to assure an aspect of variations of pharmacokinetic parameters when aminoglycoside dosing regimen was changed from TD to ODD, and evaluate if this variations were significant. The subjects of this study were 15 patients (mean age 53 ± 12, Man: Female=14:1) that administered aminoglycoside antibiotics during the period of admission in SNUH, and carried out TDM at least once at TD and at least once at ODD from January, 2003 to October, 2004. The patients presenting changes in kidney function or volume of distribution during the period from first TDM at TD to next TDM at ODD, were excluded. Pharmacokinetic parameters (Ke, Vd, CL) were calculated by Sawchuk-Zaske's method using one-compartment model, and the variations of pharmacokinetic parameters were analyzed and compared. When amioglycoside dosing regimen was changed from TD to ODD, elimination rate constant (Ke) and clearance (CL) was statistically significantly decreased (p＜0.001). The smaller Ke for TD, the larger difference from Ke for TD to Ke for ODD (y=-222.54x + 22.533, R2=0.741). But volume of distribution was not significantly changed according to aminoglycoside dosing regimen change. This result was similar to that of other studies about pharmacokinetic parameters of ODD. Consequently, it is suggested to recommend TDM for dose adjustment at ODD until aminoglycoside dosage guideline at ODD is established, based on well-controlled studies on pharmacokineitics of ODD.