| Part one Methodology determination on testing linezolid concentration in plasma and cerebrospinal fluidObjective To establish an efficient, highly sensitive, accessible high performance liquid chromatography(HPLC) method for testing determining linezolid concentration in human plasma and cerebrospinal fluid(CSF).Methods Analysis was carried out on a Zorbax ODS-SP column(4.6×250mm, 5μm) after the protein in plasma and CSF was precipitated by methanol solution; the mobile phase was consisted of acetonitrile-water(80:20, V:V), the flow rate was 1.0ml/min; the UV detection wavelength was 254 nm and the column temperature was 30℃; Sample volume 20μl.Results Linezolid concentrations in plasma samples had good linearity when they were in the range of 0.5~50μg/ml(r=0.9992), the lowerst limit of quantification was 0.5μg/ml. The relative recoveries of inezolid ranged from 97% to 103%, both the Intra and inter-daily relative standard deviation(RSD) were less than 5%. Linezolid concentrations in CSF had good linearity ranging from 0.5μg/ml to 50μg/ml( r=0.9994). The lowerst limit of quantification in CSF was 0.5μg/ml. The relative recoveries of inezolid ranged from 99% to 100%. The daytime RSD value of CSF specimen was less than 6% and inter-daily RSD value of CSF specimen was less than 5%. The experiment results showed the measurement stability of plasma and CSF samples at the following situation: at room temperature for 12 hours, being kept in the-80℃ for 20 days andbeing repeated freezing and thawing for 3 times.Conclusion The HPLC method for measuring the concentration of linezolid is sensitive, rapid, accurate and can rapidly measure linezolid concentration in plasma and cerebrospinal fluid.Part two Pharmacokinetics of linezolidin in the plasma and CSF of critically ill patientObjective To study the pharmacokinetics of linezolid in the plasma and cerebrospinal fluid of critically ill patients; To explore the precise medicine in the treatment of critically ill patient when using linezolid.Methods Collecting the data of the patients who met the inclusion criteria when adopted to the intensive care unit(ICU) and was treated with linezolid against infection;Blood samples were collected for blank control before treatment. Blood samples were taken at 0h, 0.25 h, 0.5h, 1h, 2h, 4h, 6h, 8h, 10 h, 12 h respectively after the administration of medicine completed. If patients had ventricular drainage tube, CSF samples were taken at0 h, 0.25 h, 0.5h, 1h, 2h, 4h, 6h, 8h, 10 h, 12 h after the administration of medicine completed. Using high performance liquid phase chromatographic method for the measurement of drug concentration of linezolid, and using pharmacokinetics software BAPP3.0 to calculate the pharmacokinetic parameters.Results In this study, we collected a total of 12 cases of patients with plasma samples and 4 cases with cerebrospinal fluid specimens. There were significant individual difference in plasma linezolid concentration, linezolid plasma peak concentration(Cmax) was(2.344±4.16)μg/ml and the RSD values was 17.75%;elimination half-life(T1/2β) was(405±1.79) h, AUCt was(96.84±32.49) hμg/ml, the AUC24/MIC fluctuated from 37.83 to100.05 in the patients with exact MIC values; cerebrospinal fluid(CSF) peak concentration of drug was(12.32±3.80)μg/ml, elimination half-life(T1/2) was(5.03±2.32)h, AUCt was(66.74±38.36)hμg/ml and AUCtbrain/AUCtblood was(68%±39%).Conclusion There were significant individual difference in the plasma linezolid concentration of critically patients, and monitoring plasma concentration of drug should be needed to optimize individual dosing regimen. Linezolid has a certain penetration in cerebrospinal fluid and it is possible to achieve effective therapeutic concentration in the cerebrospinal fluid under the conventional dosage regimen.But there should be more cases to establish the pharmacokinetics model of linezolid for predicting and monitoring in the treatment of precise medicine. |
PDF Full Text Request