Kirkpatrick C M, Duffull S B, Begg E J
Department of Clinical Pharmacology, Christchurch Hospital, PO Box 4710, Christchurch, New Zealand.
Br J Clin Pharmacol. 1999 Jun;47(6):637-43. doi: 10.1046/j.1365-2125.1999.00938.x.
Nine hundred and fifty-seven patients were dose-individualized for gentamicin using SeBA-GEN, a Bayesian dosing method. This method returns estimates of the values of gentamicin CL and V d from which the 24 h AUC can be estimated. The goal of therapy was to attain an AUC of 70-100 mg l-1 h depending on the severity of the infection. The population was divided into four groups of differing renal function. Linear regression analysis was performed to determine the relationship between V d and various indices of weight, and gentamicin CL and either CLCr,adjusted or CLCr,unadjusted.
The mean V d (+/-s. d.) and CL (+/-s.d.) of gentamicin in our total population were 17.4 (+/-4.1) l and 4.0 (+/-1.8) l h-1, respectively. There was a decrease in V d with reducing renal function when comparing patients with normal renal function and patients with poor renal function. The lower of total body weight (TBW) and lean body weight (LBW), termed dosing weight (DWT), was a slightly better predictor of V d (r2=0.28) than either TBW (r2=0.21) or LBW (r2=0.21). CLCr,adjusted (r2=0.80) was a better predictor of gentamicin CL than CLCr, unadjusted (r2=0.57).
The mean population values of V d and CL of gentamicin dosed once daily are similar to those described by others in relation to multiple daily dosing. Given that previous methods have been based on population values of V d and CL from multiple daily dosing, the currently recommended starting doses for once daily aminoglycoside dosing would seem appropriate. The V d reduced with decreasing renal function, with a maximum of 23% difference between patients with normal and poor renal function. The Cockcroft and Gault method of calculating creatinine clearance does not appear to perform well at low values of serum creatinine concentration. An adjustment of the Cockcroft and Gault method is proposed to allow for this.
采用贝叶斯给药方法SeBA - GEN对957例患者的庆大霉素剂量进行个体化调整。该方法可返回庆大霉素CL和Vd值的估计值，据此可估算24小时AUC。治疗目标是根据感染严重程度使AUC达到70 - 100 mg·l-1·h。将研究人群分为肾功能不同的四组。进行线性回归分析以确定Vd与各种体重指标之间的关系，以及庆大霉素CL与CLCr,调整后或CLCr,未调整之间的关系。
我们总体人群中庆大霉素的平均Vd（±标准差）和CL（±标准差）分别为17.4（±4.1）L和4.0（±1.8）L·h-1。比较肾功能正常和肾功能差的患者时，Vd随肾功能降低而降低。总体重（TBW）和瘦体重（LBW）中较低者，即给药体重（DWT），对Vd的预测性（r2 = 0.28）略优于TBW（r2 = 0.21）或LBW（r2 = 0.21）。CLCr,调整后（r2 = 0.80）比CLCr,未调整（r2 = 0.57）能更好地预测庆大霉素CL。
每日给药一次的庆大霉素的Vd和CL的平均群体值与其他人描述的每日多次给药的情况相似。鉴于先前的方法基于每日多次给药时Vd和CL的群体值，目前推荐的每日一次氨基糖苷类药物给药的起始剂量似乎是合适的。Vd随肾功能降低而降低，肾功能正常和肾功能差的患者之间最大差异为23%。Cockcroft和Gault计算肌酐清除率的方法在血清肌酐浓度较低时似乎表现不佳。为此提出了对Cockcroft和Gault方法的调整。
