Purpose: To assess the pharmacokinetics and safety of pure S-ketamine (esketamine) in Chinese patients undergoing painless gastroscopy and evaluate the potential advantage of esketamine in clinical treatment compared with racemate ketamine hydrochloride injection. Patients and methods: A randomized, open-label, parallel-controlled, Phase I study was performed with 32 patients undergoing painless gastroscopy. Patients received a single dose of esketamine (0.5 mg/kg) or racemic ketamine (1 mg/kg, esketamine:R-ketamine=1:1), injected in 10 s. Blood samples were collected for pharmacokinetic analysis. The concentrations of esketamine, R-ketamine, S-norketamine, and R-norketamine were measured with a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. Results: After administering a single dose of esketamine and racemate ketamine, the pharmacokinetics parameters of esketamine and S-norketamine are both similar in treatment groups. The clearance of esketamine in two groups was 18.1±3.2 and 18.4±3.4 mL/min•kg, respectively. However, in the ketamine group, esketamine has a larger clearance than R-ketamine (18.4±3.4 mL/min·kg vs 15.8±3.1 mL/min·kg, P<0.001). Further analysis showed that gender did not affect the pharmacokinetics of esketamine and racemate ketamine. Regarding the safety of esketamine and racemate ketamine, no serious adverse events were observed during treatment, and the incidences of adverse events were 75.0% (esketamine) and 87.5% (racemate ketamine). The main adverse reactions were dizziness, agitation, nausea, vomiting, headache, and fatigue. However, compared with racemic ketamine, esketamine offers a shorter recovery time (9 mins vs. 13 mins, P<0.05) and orientation recovery time (11.5 mins vs. 17 mins, P<0.05) after short anesthesia. Conclusion: Esketamine administration as a single dose of 0.5 mg/kg was generally safe and tolerated in patients undergoing painless gastroscopy. In terms of anesthesia, a relatively small dose of esketamine can be used instead of racemate ketamine for routine treatment without consideration of gender differences.

Genetic polymorphisms of Wnt/β-catenin pathway genes are associated with the efficacy and toxicities of radiotherapy in patients with nasopharyngeal carcinoma Genetic polymorphisms of Wnt/β-catenin pathway genes are associated with the efficacy and toxicities of radiotherapy in patients with nasopharyngeal carcinoma

Routine clinical meropenem therapeutic drug monitoring data can be applied to model-informed precision dosing. The current study aimed to evaluate the adequacy and predictive capabilities of the published models with routine meropenem data and identify the dosing adaptations using a priori and Bayesian estimation. For this, 14 meropenem models for the external evaluation carried out on an independent cohort of 134 patients with 205 meropenem concentrations were encoded in NONMEM 7.3. The performance was determined using: 1) prediction-based and simulation-based diagnostics; and 2) predicted meropenem concentrations by a priori prediction using patient covariates only; and Bayesian forecasting using previous observations. The clinical implications were assessed according to the required dose adaptations using the meropenem concentrations. All assessments were stratified based on the patients with or without continuous renal replacement therapy. Although none of the models passed all tests, the model by Muro et al. showed the least bias. Bayesian forecasting could improve the predictability over an a priori approach, with a relative bias of −11.63–68.89% and −302.96%–130.37%, and a relative root mean squared error of 34.99–110.11% and 14.78–241.81%, respectively. A dosing change was required in 40.00–68.97% of the meropenem observation results after Bayesian forecasting. In summary, the published models couldn’t adequately describe the meropenem pharmacokinetics of our center. Although the selection of an initial meropenem dose with a priori prediction is challenging, the further model-based analysis combining therapeutic drug monitoring could be utilized in the clinical practice of meropenem therapy.