Department of Clinical Pharmacy, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Ther Drug Monit. 2011 Dec;33(6):750-6. doi: 10.1097/FTD.0b013e318239a728.
Optimal use of amiodarone (AMD) requires information regarding the drug's pharmacokinetics and the influence of various factors on the drug's disposition. This study was conducted to establish the role of patient characteristic in estimating doses of AMD using nonlinear mixed effects modeling in Japanese patients treated with oral therapy.
Serum concentrations of AMD were determined by high-performance liquid chromatography. The 151 serum trough concentrations from 23 patients receiving repetitive oral AMD were collected. Analysis of the pharmacokinetics of AMD was accomplished using a 1-compartment open pharmacokinetic model. The effect of a variety of developmental and demographic factors on AMD disposition was investigated.
Estimates generated by nonlinear mixed effects modeling indicated that the clearance of AMD was influenced by the demographic variables: total body weight (TBW), daily dosage of AMD (DD), body mass index (BMI), gender (GEN), duration of AMD dosing (DUR), and patient clearance factor (Conc(θ); Conc = serum trough concentration of AMD). The final pharmacokinetic parameters were CL/F (L/h) = 0.072·TBW·Conc(-1.01)·1.95(DD≥200)·0.931(BMI≥25)·1.37(GEN)·DUR(-0.016), and Vd/F (L) = 78.4·TBW, where CL is total body clearance and Vd is volume of distribution. As all doses were given orally, it was impossible to assess the bioavailability (F). DD ≧200 is an indicator variable that has a value of 1 if the patient is receiving more than 200 mg daily dosage of AMD, and 0 otherwise. BMI ≧25 is an indicator variable that has a value of 1 if the BMI is 25 kg/m² and over, and 0 otherwise. GEN is an indicator variable that has a value of 1 if the patient is woman, and 0 otherwise.
The authors developed new population pharmacokinetic parameters. Clinical application of the findings in the present study to patient care may permit selection of an appropriate initial maintenance dose, thus enabling the clinician to achieve a desired therapeutic effect.
为了优化胺碘酮（AMD）的使用，需要了解其药代动力学信息以及各种因素对药物处置的影响。本研究旨在通过非线性混合效应模型，在接受口服治疗的日本患者中，建立患者特征在估算 AMD 剂量中的作用。
采用高效液相色谱法测定 AMD 的血清浓度。收集 23 例接受重复口服 AMD 治疗的患者的 151 个血清谷浓度。采用一室开放药代动力学模型分析 AMD 的药代动力学。研究了多种发育和人口统计学因素对 AMD 处置的影响。
非线性混合效应模型生成的估算值表明，AMD 的清除率受到以下人口统计学变量的影响：总体体重（TBW）、AMD 的日剂量（DD）、体重指数（BMI）、性别（GEN）、AMD 给药持续时间（DUR）和患者清除因子（Conc（θ）；Conc = AMD 的血清谷浓度）。最终药代动力学参数为 CL/F（L/h）= 0.072·TBW·Conc(-1.01)·1.95（DD≥200）·0.931（BMI≥25）·1.37（GEN）·DUR(-0.016），Vd/F（L）= 78.4·TBW，其中 CL 为全身清除率，Vd 为分布容积。由于所有剂量均为口服给予，因此无法评估生物利用度（F）。DD≥200 是一个指示变量，如果患者每天接受超过 200mg 的 AMD 剂量，则其值为 1，否则为 0。BMI≥25 是一个指示变量，如果 BMI 为 25kg/m² 及以上，则其值为 1，否则为 0。GEN 是一个指示变量，如果患者为女性，则其值为 1，否则为 0。
作者开发了新的群体药代动力学参数。本研究结果在临床患者护理中的应用可能允许选择合适的初始维持剂量，从而使临床医生能够达到预期的治疗效果。
Zotero 插件