Pharmacokinetics of colistin in cerebrospinal fluid after intraventricular administration alone in intracranial infections |
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Authors: | Min Ni Liang Zhao Wen-jing Zhang Jia-wei Ma Guo-yan Zhang Da-ming Cui Ke Wang Yi-bo Fei Liang Gao Fu-ming Shen |
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Affiliation: | 1. Department of Pharmacy, Shanghai Tenth People''s Hospital, Tongji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, China;2. Department of Pharmacy, Shanghai Baoshan Luodian Hospital, Shanghai, China;3. Department of Pharmacy, Inner Mongolia Autonomous Region People''s Hospital, Inner Mongolia Autonomous Region, China;4. Department of Neurosurgery, Shanghai Tenth People''s Hospital, Tongji University School of Medicine, 301 Middle Yanchang Road, Shanghai 200072, China |
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Abstract: | The aim of this study was to investigate the pharmacokinetics of colistin in cerebrospinal fluid (CSF) after intraventricular (IVT) administration of colistin methanesulfonate (CMS) for central nervous system (CNS) infections caused by multidrug-resistant Gram-negative bacteria. Ten patients with CNS infection were treated with CMS (active substance colistin equivalent to 100 000 units, every 24 h) by IVT administration. After 3 days of treatment, the concentration of colistin in the CSF was determined by selective ultra-performance liquid chromatography (UPLC) at 2, 4, 6, 8, 12 and 24 h after CMS administration. A pharmacokinetic analysis was performed using Phoenix WinNonlin. Following IVT administration of CMS, the estimated colistin apparent CSF half-life (t1/2) was 10.46 ± 6.98 h, the average peak colistin concentration (Cmax) was 16.95 ± 7.39 μg/mL and the average time to peak concentration (Tmax) was 4.6 ± 0.97 h. The measured trough concentration (Cmin; colistin concentration in CSF at 24 h after administration of CMS) was 1.12–8.33 μg/mL and the average Cmin was 2.91 ± 2.11 μg/mL. CSF concentrations of colistin were above the minimum inhibitory concentration (MIC) of 0.5 μg/mL at 24 h after IVT administration in all patients. Microbiological cure was observed in all patients. In conclusion, this is the first study of colistin pharmacokinetics in CSF after IVT administration alone in patients with CNS infection. It provides essential data for designing relatively safe and effective CMS dosing regimens. |
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