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巴基斯坦肠热病患者环丙沙星的群体药代动力学。

Population pharmacokinetics of ciprofloxacin in Pakistani patients suffering from enteric fever.

出版信息

Int J Clin Pharmacol Ther. 2021 Jan;59(1):47-54. doi: 10.5414/CP203823.

Abstract

BACKGROUND

Ciprofloxacin, a potent carboxy-fluoroquinolone is proved to be effective against some resistant strains of Gram-negative bacteria. Being a hydrophilic drug, it is primarily excreted through the kidney; almost 66% of the clearance from the body occurs through glomerular filtration. Therefore, renal status of the patient can have a significant effect on ciprofloxacin clearance.

MATERIALS AND METHODS

A total of 158 samples were collected from 32 patients treated with ciprofloxacin in the Surgical Unit-I of Lahore General Hospital, Pakistan. The data was used for the development of a population pharmacokinetic model by using non-linear mixed-effect modeling (NONMEM) software. The influence of different covariates (age, sex, body weight, serum creatinine (SeCR), and creatinine clearance (CRCL)) was observed on ciprofloxacin clearance (CL) and volume of distribution (Vd) by stepwise covariate modeling (SCM).

RESULTS

A one-compartment model was used for ciprofloxacin population pharma-cokinetik (popPK) analysis, and the values for ciprofloxacin CL and Vd in the final model were estimated at 19.8 L/h and 74.9 L, respectively. Among all the tested covariates, only CRCL was proven to have significant influence on ciprofloxacin CL.

CONCLUSION

A strong relationship was found between the ciprofloxacin CL and renal status of the patients. The model can be used for dose tailoring in patients based on their CRCL values before the start of therapy with ciprofloxacin among Pakistani patients.

摘要

背景

环丙沙星是一种有效的羧基-氟喹诺酮类药物,已被证明对一些耐革兰氏阴性菌的菌株有效。作为一种亲水性药物,它主要通过肾脏排泄;大约 66%的清除率来自肾小球滤过。因此,患者的肾脏状况对环丙沙星的清除率有显著影响。

材料和方法

从巴基斯坦拉合尔总医院外科 I 病房接受环丙沙星治疗的 32 名患者中收集了总共 158 个样本。使用非线性混合效应建模(NONMEM)软件,使用这些数据开发了一个群体药代动力学模型。通过逐步协变量建模(SCM)观察不同协变量(年龄、性别、体重、血清肌酐(SeCR)和肌酐清除率(CRCL))对环丙沙星清除率(CL)和分布体积(Vd)的影响。

结果

使用单室模型进行环丙沙星群体药代动力学(popPK)分析,最终模型中环丙沙星 CL 和 Vd 的值分别估计为 19.8 L/h 和 74.9 L。在所有测试的协变量中,只有 CRCL 被证明对环丙沙星 CL 有显著影响。

结论

发现环丙沙星 CL 与患者的肾脏状况之间存在很强的关系。该模型可用于根据巴基斯坦患者开始环丙沙星治疗前的 CRCL 值,对患者进行剂量调整。

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