Garrelts J C
Department of Pharmacy, St. Francis Campus, Wichita, Kansas 67214, USA.
Pharmacotherapy. 1996 Mar-Apr;16(2):286-94.
To simulate peak and trough concentrations, using Bayesian forecasting, achieved with a variety of once-daily dosing (ODD) regimens; to evaluate dosing regimens required to produce target peak and trough concentrations; to compare the peak-to-MIC (minimum inhibitory concentration) ratios and time above MIC for various dosing regimens and MICs; to stratify the information based on renal function estimates; and to use the results from these simulations to make recommendations regarding optimum ODD of aminoglycosides.
Simulation of ODD using a Bayesian technique and existing patient data.
A tertiary referral, community teaching hospital.
One hundred consecutive adults from the author's data base, with a wide variety of infections and underlying illnesses, who met strict inclusion criteria.
Two methods of dosing, weight-based (4-7 mg/kg) and target concentration-based (peak 10, 15, or 20 mu g/ml, trough < or = 0.3 mu g/ml), were evaluated. Each patient had a known dosing-sampling history, stable renal function, and at least two measured serum concentrations, and were being treated with either gentamicin or tobramycin.
A wide range of peak and trough serum concentrations are achieved when dosages are chosen based on patient weight. Even with large dosages, some patients had very low peak-to-MIC ratios and time above the MIC, and vice versa. Variations in MIC had a much greater effect on dosing target values than did variations in dosage. A large degree of variability was also noted in doses and dosing intervals when using a target serum concentration approach. For both methods, an inverse relationship existed between calculated creatinine clearance and time above MIC, although there was little change over the range of 60-119 ml/minute.
Bayesian simulation showed that weight-based ODD of aminoglycosides did not produce clinically acceptable serum concentrations or target values in many patients. Young and elderly patients, and any patient with a creatinine clearance below 60 or above 119 ml/minute, are especially likely not to achieve an optimum serum concentration profile. Aminoglycoside ODD should be individualized by evaluating the peak-to-MIC ratio, time above MIC, and patient response.
使用贝叶斯预测方法模拟多种每日一次给药（ODD）方案所达到的峰浓度和谷浓度；评估产生目标峰浓度和谷浓度所需的给药方案；比较各种给药方案和最低抑菌浓度（MIC）下的峰浓度与MIC之比以及高于MIC的时间；根据肾功能估计值对信息进行分层；并利用这些模拟结果就氨基糖苷类药物的最佳每日一次给药提出建议。
使用贝叶斯技术和现有患者数据对每日一次给药进行模拟。
一家三级转诊社区教学医院。
从作者的数据库中选取连续100名成年人，他们患有多种感染和基础疾病，且符合严格的纳入标准。
评估了两种给药方法，即基于体重（4 - 7mg/kg）和基于目标浓度（峰浓度10、15或20μg/ml，谷浓度≤0.3μg/ml）。每位患者都有已知的给药 - 采样史、稳定的肾功能以及至少两次测量的血清浓度，并且正在接受庆大霉素或妥布霉素治疗。
当根据患者体重选择剂量时，可实现广泛的峰血清浓度和谷血清浓度范围。即使使用大剂量，一些患者的峰浓度与MIC之比和高于MIC的时间也非常低，反之亦然。MIC的变化对给药目标值的影响远大于剂量的变化。在使用目标血清浓度方法时，剂量和给药间隔也存在很大程度的变异性。对于两种方法，计算的肌酐清除率与高于MIC的时间之间存在反比关系，尽管在60 - 119ml/分钟范围内变化不大。
贝叶斯模拟表明，氨基糖苷类药物基于体重的每日一次给药在许多患者中并未产生临床可接受的血清浓度或目标值。年轻和老年患者，以及任何肌酐清除率低于60或高于119ml/分钟的患者，尤其可能无法实现最佳血清浓度曲线。氨基糖苷类药物的每日一次给药应通过评估峰浓度与MIC之比、高于MIC的时间以及患者反应来个体化。
