庆大霉素在小鼠的时辰毒性及时辰药代动力学

本文研究了庆大霉素对小鼠的毒性及其药代动力学的昼夜节律性变化。雄性ICR小鼠自实验前两周置于标准的明期和暗期下饲养,自由进食进水。毒性实验剂量为庆大霉素290mg/kg,Sc:药代动力学实验剂量为45 mg/kg,Sc。结果表明,庆大霉素毒性及药代动力学因用药时间不同呈明显的昼夜节律性变化。明期中点用药毒性最大,血药浓度最高,AUC值最大:暗期用药毒性小,血药浓度低,AUC值小。提示了庆大霉素毒性的昼夜节律变化与其药代动力学的的昼夜节律变化有密切关系。     

庆大霉素个体化给药方案系统的临床研究

本文报告了5例男性病员应用庆大霉素个体化给药方案系统的结果,每一病例给予庆大霉素8或12万u,半小时或1小时静脉恒速滴注,在首次和再次给药后不同时间采血样,用微生物测定法测得血浓,经个体化给药方案电脑程序,按双室开放模型运算,求得各个病人个体动力单参数及预报血浓值,并向临床推荐个体化给药方案,本组病例血浓实测值与预报值的差值,峰浓为—0113±0.15,谷浓为—0.24±0.25,5病例共进行剂量调整7例次,其中不变2例次,减少3次,应增加但未改变2例次,本系统推荐的个体化给药方案及进行临床疗效分析与病员实际情况相符     

微机预测庆大霉素的临床个体化给药方案

本文用微机预测呼吸系统感染病人庆大霉素个体化给药方案,用FPIA法测定庆大霉素血药浓度。26例病人预测的个体化剂量为120±20mg,预测的峰、谷浓度分别为8.41±0.94μg/ml和0.38±0.29μg/ml,与实测值8.01±1.97μg/ml和0.34±0.36μg/ml相比无显著差异(P>0.05)。用Bayesian两点法估算的药动学参数为:消除t_(1/2) 2.68±0.88h,Vd0.2733±0.0594L/kg,总清除率75.19±19.90ml/h.kg。     

肾功能损害个体化给药

肾功能损害个体化给药李荣凌，罗顺德，陈志明（湖北省人民医院武汉４３００６０）大部分药物是通过肾脏排泄的，肾功能损害必然使药物排泄速率降低，半衰期延长，如按正常给药方案给药，就会造成蓄积中毒。因此必须调整给药方案，根据肾功能损害程度和病人生理因素实行个...     

肥胖患者体内药代动力学变化及给药方案制定

笔者查找近年国内外相关文献,对肥胖群体体内药物动力学变化进行综述,并对常用药物的给药方案进行评价。结果表明,肥胖患者体内药物分布和代谢均发生改变,从而导致给药剂量的变化,应根据肥胖患者的特点合理应用药物,提高治愈率,减少不良反应的发生,实现个体化给药。     

阿糖胞苷不同给药途径的药代动力学研究

本文报道25例急性白血病应用HPLC法对Ara-C不同给药途径的药代动力学进行了研究。结果表明:不论何种给药途径Ara-C总体清除率及浓度时间曲线下面积的平均值无差异(P>0.05)。静脉快进推注、肌肉注射及皮下注射给药可使血浆Ara-C浓度达较高水平,但峰值持续时间短、下降快。持续静脉给药,血浆Ara-C维持在30～60ng/ml范围内;持续皮下滴注时维持在30～50ng/ml范围内。髓内用药与静脉用药其药代方式一致。     

Nomogram for modification of dosage regimens in patients with chronic renal function impairment

A nomogram is presented for modifying dosage regimens of drugs administered to patients with chronic renal function impairment. The usefulness and limitations of the nomogram are discussed in terms of the objectives of dosage regimens. The nomogram is intended to serve as a guide for drug administration in patients with renal disease. It may be particularly helpful for drugs on which little or no definitive research has been undertaken.     

Comparison of pharmacokinetics and dynamics of two dosage regimens of foscarnet in AIDS patients with Cytomegalovirus retinitis

Objective: To compare the pharmacokinetics of foscarnet administered as an infusion twice daily (BID) or thrice daily (TID), and to compare the effects on the electrolyte balance, cardiac and renal functions over a 3-week induction treatment of Cytomegalovirus (CMV) retinitis. Methods: Pharmacokinetics/dynamics of foscarnet were investigated on treatment days 1, 14 and 21. Twelve AIDS patients with CMV retinitis completed the investigation period. Concentrations of foscarnet and electrolytes were assayed by high-performance liquid chromatography (HPLC) and by an ion-selective analyser, respectively. Results: The pharmacokinetics of the two regimens were essentially similar. Foscarnet plasma and creatinine clearances were 2.0 and 1.6 ml · min⁻¹ · kg⁻¹, respectively, in the BID group at steady state (day 21). In the TID group the corresponding values were 1.8 and 1.7 ml · min⁻¹ · kg⁻¹, respectively. In both regimens the elimination half-life of foscarnet was 2–3 h. Ionized calcium concentrations were transiently decreased and strongly inversely correlated to foscarnet plasma concentrations in both regimens with no significant differences between groups. A trend towards prolongation of the QTc interval was seen when data from both treatments were analysed together. Conclusion: Our data suggest comparable pharmacokinetics of foscarnet after intermittent administration BID or TID during a 3-week induction period. Received: 22 January 1996 / Accepted in revised form: 6 November 1996     

多黏菌素类药物的肾毒性及其优化给药方案研究进展

多重耐药及泛耐药革兰阴性菌的流行给临床抗感染治疗带来了巨大挑战.由于新型抗菌药物研究开发缓慢,多黏菌素这类曾因严重的神经毒性和肾毒性而逐渐停止使用的抗生素又重回人们视野,并成为了治疗重症难治性革兰阴性菌感染的主要药物.然而,肾毒性仍严重影响此类药物的临床治疗效果.其肾毒性机制复杂,并且临床上存在着许多肾毒性危险因素,因...     

接受连续性静脉-静脉血液滤过患者左氧氟沙星抗感染方案的优化

目的:对ICU肾衰竭接受连续性静脉-静脉血液滤过(continuous veno-venous haemofiltration,CVVH)治疗患者左氧氟沙星给药方案进行优化。方法:根据左氧氟沙星药效学及药动学参数等实验数据资料,应用蒙特卡洛模拟法计算累积反应分数(CFR),推荐最佳给药方案。结果:ICU肾衰竭接受CVVH治疗的患者,治疗肺炎克雷伯菌和肺炎链球菌感染时左氧氟沙星的最佳方案分别为500 mg qd iv和200 mg qd iv;ICU肾功能正常患者,对肺炎链球菌感染时左氧氟沙星的最佳方案为750 mg qd iv。对于肾衰竭或肾功能正常患者,当感染铜绿假单胞菌和金黄色葡萄球菌时,左氧氟沙星4种静注给药方案(200,300,500,750 mg qd)治疗效果均不佳,建议联合治疗或更换药物。结论:与ICU肾功能正常患者对比,ICU肾衰竭接受CVVH治疗患者使用左氧氟沙星时应根据不同病原菌感染考虑降低给药剂量。     

Pharmacokinetics of gentamicin in 957 patients with varying renal function dosed once daily

AIMS: 1. To determine the population pharmacokinetics of gentamicin in 957 patients with varying renal function dosed once daily. 2. To see if current starting doses for once daily aminoglycoside dosing are appropriate. 3. To test whether calculating creatinine clearance using an adjusted Cockcroft and Gault method (CLCr,adjusted ) was a better predictor of gentamicin clearance than the standard Cockcroft and Gault method (CLCr,unadjusted ). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.     

Bayesian一点法研究心衰患者的地高辛临床药物动力学及给药方案

本文用放免分析法测定血药农度。用Ｂａｙｅｓｉａｎ—点法研究３４例心衰患者的地高辛临床药动学，参数为：消除半衰期（Ｔ１／２）６０．８±１２．２ｈ，消除速度常数（ｋ）０．０１１９±０．００２３ｈ－１，分布容积（Ｖｄ）７．５±１．１Ｌ／ｋｇ，清除率（ＣＬ）８９．７±２０．９ｍｌ·ｈ－１．ｋｇ－１。显示患者个体存在较大差异。按Ｂａｙｅｓｉａｎ个体参数计算给药方案，所有患者的血药浓度始终维持在０．８～２．０ｎｇ／ｍｌ有效范围内。数据分析表明，在缺乏监测的条件下，可根据患者的血清肌酐水平作出剂量判断，Ｃｒ≤９０μｍｏｌ／Ｌ为０．２５ｍｇｑｄ，Ｃｒ＞９０μｍｏｌ／Ｌ为０．１２５ｍｇｑｄ。     

Pharmacokinetics of dosing regimens which utilize multiple intravenous infusions: Gentamicin in burn patients

A general approach to the establishment of dosing regimens for drug administration by multiple intravenous infusions is presented. The method is applicable where the elimination kinetics are first order and can be represented by a one-compartment open model. The approach utilizes serum concentration-time data obtained during any dosing interval for the calculation of the apparent distribution volume and the half-life in individual patients. These values are then used to individualize the dosing regimen where it is required to maintain serum concentrations of the drug within a desired range. Estimation of kinetic parameters for gentamicin in burn patients with normal or only slightly reduced renal function demonstrates a relatively constant distribution volume of 0.25 ± 0.086 liter/kg (mean ± sd)but a relatively variable half-life of 2.1 ± 1.3 hr. This finding supports the view that gentamicin regimens should be individualized even in patients with essentially normal renal function.NIH Grant RR-267 supported our use of the computer within the Health Computer Sciences Facility at the University of Minnesota.     

The safety of cefuroxime and gentamicin in patients with reduced renal function

Summary

The glomerular and tubular function of 7 patients with a spectrum of renal impairment was measured before, during and after 4-days' treatment with cefuroxime and gentamicin. Neither the mean plasma urea nor creatinine concentrations of the group increased after combined treatment, nor was the excretion of cefuroxime slowed. The ability to acidify and to concentrate the urine did not change. In only 1 patient did plasma creatinine increase and GFR fall. This patient had an unexpectedly high plasma gentamicin concentration and was taking frusemide. However, an eighth patient with acute renal failure caused by bacteraemic shock rapidly recovered renal function while being treated with cefuroxime and gentamicin for 15 days after large doses of frusemide intravenously. This limited study suggests that the useful combination of cefuroxime and gentamicin need not be denied to patients with reduced renal function, but emphasizes that the plasma gentamicin concentration must always be monitored.     

Aminoglycoside dosage adjustment in renal failure: A hand-held calculator program

Summary Several problems occur when devising dosage guidelines for aminoglycoside antibiotics in patients with renal failure. To rationally address these problems, dosage guidelines require several steps involving complex calculations, use of graphic charts and/or use of sophisticated computer systems. We describe a practical program for modifying doses of aminoglycosides using a programmable hand-held calculator; this program is based both on pharmacokinetic theory and on applicability to varied clinical settings. The program compiles a series of equations to provide recommended doses, dosing intervals and predictions of serum concentrations of aminoglycosides at various times after a dose. It is hoped that patient care can be improved by using this simple, convenient and low-cost approach which retains efficiency and accuracy as a bed side method of dosage adjustment for aminoglycosides.