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Aims: This study aims to establish a population pharmacokinetic (PK) model of teicoplanin in Chinese adult patients to evaluate the dosing regimen in the label sheet and optimize it. Methods: Nonlinear mixed‐effects modelling was used to estimate PK parameters. Monte Carlo simulations were used to evaluate the attainment of various dosing regimens in achieving the target trough concentrations in patients with normal or decreased renal function. Results: A total of 115 patients were enrolled in this retrospective study. Creatinine clearance (CrCL) and albumin (ALB) were identified as covariates on the clearance of teicoplanin. For the treatment of non‐complicated methicillin‐resistant Staphylococcus aureus (MRSA) infections in patients with normal renal function and serum ALB concentration, the recommended dosing regimen was 600 mg q12h with five administrations as the loading dose followed by 600 mg qd as the maintenance dose; for the treatment of serious and/or complicated MRSA infections, the recommended dosing regimen was 800 mg q12h with five administrations as the loading dose followed by 800 mg qd as the maintenance dose. It is worth noting that both the loading and maintenance doses ought to be modified based on the patient's renal function and serum ALB concentration. In addition, trough concentrations of teicoplanin were significantly increased every other week. Conclusions: Both loading dosing and maintenance dosing regimens were recommended to be adjusted according to patient's renal function and serum ALB concentration. In addition, it is necessary to perform follow‐up therapeutic drug monitoring of teicoplanin at least once every week. [ABSTRACT FROM AUTHOR]

Aims: Data regarding clinical pharmacokinetic/toxicodynamic (PK/TD) of polymyxin B is short of direct quantitative data. This study aims to investigate the risk factors of polymyxin B associated acute kidney injury (AKI) and to assess the relationship between polymyxin B plasma levels and its nephrotoxicity. Methods: A retrospective study was performed in adult patients treated with polymyxin B. Risk factors associated with AKI and plasma trough concentrations of polymyxin B were identified via medical record review. A multivariate logistic regression model was established and the risk of polymyxin B‐associated AKI were predicted by a receiver operating characteristic curve, with maximal Youden index used to identify safety thresholds among the study population. Results: Fifty‐four adult patients were included in the study. AKI was detected in 14 patients during polymyxin B treatment (25.9%, 14 out of 54). Cmin (odds ratio [OR] 2.071; 95% confidence interval [CI] 1.235–3.472) and baseline serum creatinine (OR 1.024; 95% CI 1.005–1.043) were significant independent risk factors for developing AKI. The area under the ROC curve of the combined predictor was larger based on the above factors. When the Youden index was at maximum, the optimal cut‐off point was 6.678 of the ROC curve. When Cmin ≥ 3.13 mg/L, the probability of AKI was more than 50%. Conclusion: In this study, when the calculated combined predictor value was >6.678, there was an increased risk of AKI. Maintaining a polymyxin B Cmin level below 3.13 mg/L may be helpful in reducing the incidence of polymyxin B associated nephrotoxicity. [ABSTRACT FROM AUTHOR]

Aims: Current FDA‐approved label recommends that the dosage of polymyxin B should be adjusted according to renal function. However, the correlation between polymyxin B pharmacokinetics (PK) and creatinine clearance (CrCL) is poor. This study aimed to develop a population PK model of polymyxin B in adult patients with various renal functions and to identify a dosing strategy. Methods: A retrospective PK study was performed in 32 adult patients with various renal function. Nonlinear mixed effects modelling was applied to build a population PK model of polymyxin B followed by Monte Carlo simulations which designed polymyxin B dosing regimens across various renal function. Results: Polymyxin B PK analyses included 112 polymyxin B concentrations at steady state from 32 adult patients, in which 71.9% of them were critically ill. In the final PK model, CrCL was the significant covariate on CL (typical value 1.59 L/h; between‐subject variability 13%). The mean (SD) individual empirical Bayesian estimate of CL was 1.75 (0.43) L/h. In addition, a new dosing strategy combining the PK/pharmacodynamic (PD) targets and Monte Carlo simulation indicated that the reduction of polymyxin B dose in patients with renal insufficiency improved the probability of achieving optimal exposure. For severe infections caused by organisms with minimum inhibitory concentration (MIC) ≥ 2 mg/L, a high daily dose of polymyxin B might be possible for bacterial eradication, but the risk of nephrotoxicity is increased. Conclusions: Renal function plays a significant role in polymyxin B PK, and the dose of polymyxin B should be adjusted according to CrCL in patients with renal insufficiency. [ABSTRACT FROM AUTHOR]

Ougan (Citrus suavissima Hort. ex Tanaka) is an important domesticated fruit which is used medicinally in China. To date, a number of methods for its identification and chemical analysis have been studied. However, the effects of Ougan juice on CYP isozymes have not been reported. Therefore, the objective of our study was to evaluate the potential effects of Ougan juice on the CYP isozymes CYP1A2, CYP2C9, CYP2C19 and CYP2D6 in rats using a cocktail approach involving the probe drugs phenacetin, tolbutamide, omeprazole and dextromethorphan. These four probe drugs were simultaneously administered to rats after single and multiple dosing of Ougan juice by gastric irrigation. The pharmacokinetics of the probes in the plasma were simultaneously determined by HPLC-MS. The main pharmacokinetic parameters of the four probe drugs were not significantly different in rats after single dose of Ougan juice. The t1/2 and AUC(0-infinity) of phenacetin and omeprazole increased significantly and their CL(z) decreased markedly after multiple dosing of Ougan juice. However, the t1/2 of tolbutamide decreased notably, while the t1/2 of dextromethorphan was not changed. The findings of this study suggest that a single administration of Ougan juice had little effect on P450 activities while multiple administration of Ougan juice tended to inhibit CYP1A2 and CYP2C19 and induce CYP2C9, but did not influence CYP2D6.

Objective: To develop a method for determination of clozapine, olanzapine and mirtazapine in human plasma by liquid chromatography-tandem mass spectrometry(LC-MS/MS)., Methods: Clozapine, olanzapine and mirtazapine were extracted from plasma samples by using diethyl ether and separated by Agilent Zorbax SB-C18 column(2.1 mm x 150 mm, 5 microm). Electrospray ionization source was applied, positive ion mode was used to detect and multiple reaction monitoring mode was used to quantify clozapine, olanzapine and mirtazapine. Carbamazepine was the internal standard., Results: The detection limits of clozapine, olanzapine and mirtazapine were within 0.41-0.92 ng/mL. The calibration curve in the concentration range of 10.0-2000.0 ng/mL showed a good linear distribution (r > or = 0.992 4). The average extraction recoveries were within 65.7%-94.2%. Intra-day RSD and inter-day RSD were less than 6% (n = 5)., Conclusion: This method seems to be quite specific, sensitive and accurate, and can be used to detect clozapine, olanzapine and mirtazapine in forensic and clinical analytic toxicology.