A first-in-human study of Brozopentyl Sodium, following single and multiple ascending intravenous infusion in Chinese healthy volunteers.

BACKGROUND: Brozopentyl Sodium (BZP), a novel agent for ischemic stroke, has shown promising results in preclinical pharmacological studies, prompting the initiation of the first-in-human investigation. PURPOSE: This study aimed to assess the safety, tolerability, and pharmacokinetic (PK) characteristics of BZP in Chinese healthy volunteers. METHODS: The study consisted of two parts. Part I was a single-center, randomized, single-blinded, placebo-controlled, single-ascending study with six BZP dose cohorts (SAD: 25, 50, 100, 200, 300, and 400 mg). Part II was a single-center, randomized, single-blinded, placebo-controlled, multi-dose- and dose-elevated study with three BZP dose cohorts (MAD: 50, 100, and 200 mg). Doses were administered once daily on days 1 and 7 and twice daily on days 2-6. The PK properties of BZP and its bioactive metabolites, BNBP, were assessed. Safety and tolerability evaluations were also conducted. RESULTS: In the SAD study, BZP reached peak plasma concentrations (Tmax) at the end of administration, with median Tmax values ranging from 1 to 1.03 h, while BNBP reached Tmax between 1.25 to 1.38 h. The terminal half-lives (T1/2) were approximately 8 h for BZP and 15 h for BNBP. In the MAD study, steady-state plasma concentrations of BZP were reached by day 5. There was minimal accumulation of both BZP and BNBP after 7 days of administration. The area under the plasma concentration-time curve from 0 to time of the last measurable concentration (AUC0-t) and maximum plasma drug concentration (Cmax) showed dose-proportional increases for BZP but not for BNBP in both study parts. Single and multiple doses of BZP demonstrated a good safety profile and were well-tolerated. CONCLUSION: BZP displayed safety, good tolerability and predictable PK characteristics following both single and multiple ascending intravenous administrations. These findings provide a basis for further clinical development of BZP for ischemic stroke patients.

Safety, tolerance, pharmacokinetic and pharmacodynamic properties of thrombopoietin mimetic peptide for injection in Chinese healthy volunteers: a randomized, placebo-controlled, double-blind study.

The thrombopoietin mimetic peptide for injection is a second-generation thrombopoietin receptor agonist (TPO-RA) used in the treatment of patients with immune thrombocytopenia. The aim of the present study was to assess the safety, tolerance, pharmacokinetic and pharmacodynamic properties of thrombopoietin mimetic peptide for injection in Chinese healthy volunteers. A randomized, placebo-controlled, double-blind, dose-escalation study was conducted in healthy Chinese subjects aged 18-50 years. Thirty subjects received single subcutaneous injection of 0.3 µg/kg, 1.0 µg/kg, 2.0 µg/kg thrombopoietin mimetic peptide or placebo. Thrombopoietin mimetic peptide was safe and well tolerated at doses of 0.3-2.0 µg/kg. There was no significant change in mean platelet count (PLT) from baseline at the 0.3 µg/kg or placebo groups. The mean PLT of subjects in the 1.0 µg/kg and 2.0 µg/kg groups peaked at day 12 (± 1), began to decline around day 17, and returned to the baseline level at day 28 (± 1). Platelet aggregation rates of the three dose groups showed no significant change before and after administration. Serum concentrations of thrombopoietin mimetic peptide in all subjects were below the quantization limit. This was the first study to demonstrate that subcutaneous injection of thrombopoietin mimetic peptide at doses of 0.3-2.0 µg/kg was safe and well tolerated in Chinese healthy subjects. As a second-generation TPO-RA, thrombopoietin mimetic peptide is effective at improving PLT after single subcutaneous injection at dose of ≥1 µg/kg.P lain l anguage s ummaryWhat is the context?● Immune thrombocytopenia (ITP) is a rare, serious autoimmune disorder characterized by low platelet count (PLT) without an alternate cause. The treatment goal of ITP is to increase the platelet count to a safe level that can stop active bleeding and reduce the risks of future bleeding.● Thrombopoietin receptor agonists (TPO-RAs, e.g. eltrombopag, avatrombopag, hetrombopag, and romiplostim) have shown high response rates in stimulating platelet production and reducing the risk of bleeding. TPO-RAs provide ITP patients with well-tolerated, long-term treatment choices.What is new?● The thrombopoietin mimetic peptide for injection is a new TPO-RAs developed by Shandong Quangang Pharmaceutical Co., Ltd. (China).● This study showed that thrombopoietin mimetic peptide is effective at improving PLT after a single subcutaneous injection.● The thrombopoietin mimetic peptide is safe and well-tolerated in Chinese healthy subjects.What is the impact?● This study provides evidence for the further development potential of the thrombopoietin mimetic peptide.

High-Dose Clopidogrel versus Ticagrelor in CYP2C19 intermediate or poor metabolizers after percutaneous coronary intervention: A Meta-Analysis of Randomized Trials.

WHAT IS KNOWN AND OBJECTIVE: For patients after percutaneous coronary interventions (PCI), clopidogrel combined with aspirin is a conventional dual antiplatelet therapy (DAPT) method. Because the genetic polymorphism of CYP2C19 gene leads to clopidogrel resistance, guidelines for antiplatelet recommendations in CYP2C19 of ultrarapid metabolizers (UM), extended metabolizers (EM) and poor metabolizers (PM) are clear. However, there is no clear recommendation as to whether ticagrelor or double dose clopidogrel is the best antiplatelet regimen for CYP2C19 of intermediate metabolizers (IM). To evaluate the efficacy and safety of ticagrelor (combined with aspirin) and high-dose clopidogrel (combined with aspirin) in patients after PCI with CYP2C19 loss-of-function (LOF) alleles. METHODS: We searched the following databases to select RCTs of comparing ticagrelor with high-dose clopidogrel in patients after PCI with CYP2C19 LOF alleles: CNKI, Wanfang Data, PubMed, Clinical trials, Cochrane, Web of Science and Embase. Major adverse cardiovascular events (MACEs), platelet function and TIMI bleeding event were defined as the outcomes. revman 5.3 software was used to perform meta-analysis. RESULTS AND DISCUSSION: A total of 14 RCTs with 2351 patients were enrolled. Meta-analysis showed that compared with high-dose clopidogrel, ticagrelor had reduced incidence of MACEs (OR = 0.32, 95% Cl: 0.23-0.44, p < 0.00001), stent thrombosis (OR: 0.24, 95%CI: 0.13-0.44, p < 0.00001), myocardial infarction OR: 0.42, 95%CI: 0.22-0.80, p = 0.008), revascularization (OR: 0.29, 95%CI: 0.10-0.82, p = 0.02) and unstable angina (OR: 0.47, 95%CI: 0.29-0.77, p = 0.003) in patients after PCI with CYP2C19 LOF alleles. A subgroup analysis showed that ticagrelor reduced the risk of MACEs compared with high-dose clopidogrel regardless of the type of metabolizer. Compared with high-dose clopidogrel, ticagrelor significantly reduced the risk of MACE with longer follow-up period (more than 3 months) without increasing the risk of bleeding (OR: 0.89, 95%CI: 0.53-1.49, p = 0.30), while elevated dyspnoea (OR: 5.62, 95%CI: 3.07-10.28, p < 0.00001). WHAT IS NEW AND CONCLUSIONS: For patients carrying CYP2C19 LOF alleles after PCI, ticagrelor may be better than high-dose clopidogrel in reducing the risk of MACEs, while dyspnoea incidents should be alerted.

Pharmacokinetics, Safety, and Tolerability of Single- and Multiple-Dose Once-Daily Baricitinib in Healthy Chinese Subjects: A Randomized Placebo-Controlled Study.

The objective of this phase 1 study was to evaluate the pharmacokinetics, safety, and tolerability of baricitinib after single and multiple doses in healthy Chinese adults. Eligible subjects received a once-daily dose of baricitinib 2, 4, or 10 mg or placebo on day 1 (single dose) and days 4 through 10 for 7 consecutive days (multiple doses). Plasma pharmacokinetic samples were collected up to 48 hours after dosing on days 1 and 10, with predose samples collected before dosing on day 1 and days 4 through 10. Safety and tolerability were also assessed. Baricitinib was rapidly absorbed, reaching peak plasma concentrations within 0.5 to 1 hour (median). Plasma concentrations declined rapidly following the attainment of peak concentrations, with a mean terminal half-life of 5.7 to 7.3 hours. Steady-state plasma concentrations of baricitinib were achieved after the second day of once-daily dosing, with minimal accumulation of baricitinib in plasma (up to 10% increase in area under the plasma concentration-time curve). Single- and multiple-dose mean values for area under the plasma concentration-time curve from time zero to infinity and maximum plasma concentration appeared to increase in an approximately dose-proportional manner across the dose range. Single and multiple oral doses of once-daily baricitinib up to 10 mg were well tolerated by healthy Chinese subjects.

Safety, pharmacokinetic and pharmacodynamic properties of single ascending dose and continuous infusion of remimazolam besylate in healthy Chinese volunteers.

PURPOSE: The aim of the present study was to evaluate the safety, pharmacokinetic (PK) and pharmacodynamic (PD) properties of remimazolam besylate following single ascending dose (SAD) and continuous infusion in healthy Chinese volunteers. METHODS: This was a randomized phase I study conducted in two parts. Part I was a double-blind, placebo- and midazolam-controlled, SAD study among healthy Chinese participants with a remimazolam dose of 0.025-0.4 mg/kg. Part II was an open-label, midazolam-controlled, continuous infusion study. Bispectral index (BIS) monitoring and Modified Observers Assessment of Alertness and Sedation (MOAA/S) score assessment were used to assess the PD properties. RESULTS: The half-life range of remimazolam was from 34.1 ± 8.1 to 59.8 ± 20.5 min in the SAD study. The sedation function was initially observed at the dose of 0.05 mg/kg remimazolam. Doses of ≥ 0.075 mg/kg exerted a peak sedation effect within 1-2 min after injection, resulting in a deeper and more rapid sedation. In the 2 h continuous infusion, remimazolam showed a deeper sedation and more rapid recovery than midazolam. For general anesthesia, an induction dosage of 0.2 mg/kg/min and a maintenance dosage of 1 mg/kg/h can achieve a satisfactory efficacy effect. CONCLUSIONS: Remimazolam was safe and well tolerated in healthy Chinese participants. Based on the phase I clinical study, we suggest that remimazolam besylate demonstrates greater sedation and quicker recovery from sedation than midazolam.

Population pharmacokinetics of vancomycin in Chinese infants
.

OBJECTIVE: To determine the pharmacokinetics (PK) of vancomycin in Chinese infant patients using a population pharmacokinetic (PKK) approach in order to provide support for individualized vancomycin therapy. METHOD: The data included 72 sets of steady-state peak and trough serum concentrations from 61 infants (0 - 1 years). PPK analysis was performed using the nonlinear mixed-effects modeling software. Inter- and intraindividual variability was estimated for the clearance and distribution volume of vancomycin. The potential effects of patient sex, postnatal age, postconceptional age, height, weight, body surface area, body mass index, alanine aminotransferase, aspartate aminotransferase, total protein, albumin, white blood cell count, serum creatinine, and concomitant medications on vancomycin PKs were explored. RESULTS: A one-compartment linear model with first-order elimination was used to describe the data. Weight and postnatal age had a significant influence on vancomycin clearance. The typical population parameter estimates of clearance and distribution volume were 0.46 L/h and 4.45 L, respectively. Goodness-of-fit plots and bootstrap outcomes confirmed the relatively good stability and prediction capability of the model. CONCLUSION: This study initially established a vancomycin PPK model to estimate individual PK parameters in Chinese infant patients.
.

Saliva and Plasma Monohydroxycarbamazepine Concentrations in Pediatric Patients With Epilepsy.

BACKGROUND: Monohydroxycarbamazepine (MHD, 10-hydroxy-carbamazepine) is the main active metabolite of oxcarbazepine (OXC). The present study aims to investigate the relationship between plasma and saliva concentrations of MHD in Chinese children with epilepsy. METHODS: Plasma and saliva samples were collected and MHD levels were measured by high-performance liquid chromatography system. Linear regression analysis was conducted between the dose of OXC and saliva concentrations, between the dose of OXC and plasma concentrations, and between the saliva concentrations and plasma concentrations. Student's t-test was used for unpaired data. A one-way analysis of variance was used for analyzing co-medication in subgroups of patients. RESULTS: A total of 58 blood samples and 58 saliva samples were obtained from 52 pediatric epileptic patients, with a median age of 5.67 years (0.58-15 years, 23 males and 29 females). There was an apparent positive correlation between the plasma and saliva MHD concentrations [Y = 0.77x - 0.85 (n = 58), R = 0.908, P < 0.01]. MHD plasma and saliva concentrations were positively correlated to daily drug dose (r = 0.461 and 0.417; P < 0.01 respectively). The saliva/plasma MHD ratio was around 0.71 and had no significant difference with age, gender, and combined medications. When data were analyzed for subgroups (one group taking OXC as monotherapy, the second group taking OXC in add-on with non-enzyme-inducing antiepileptic drugs, and the third group taking OXC in add-on with hepatic-enzyme-inducing antiepileptic drugs or moderate inducers), no significant difference was found between plasma and saliva MHD concentrations in all the above 3 groups. CONCLUSIONS: High correlation between plasma and saliva MHD levels supported the use of saliva as an alternative to plasma for OXC monitoring in children with epilepsy.

Metformin versus insulin for gestational diabetes mellitus: a meta-analysis.

The aim of the present meta-analysis was to determine the efficacy and safety of metformin for the treatment of women with gestational diabetes mellitus (GDM). We searched databases, including PubMed, Embase and the Cochrane Central Register of Controlled Trials, for randomized controlled trials (RCTs) comparing metformin and insulin treatments in women with GDM. We carried out statistical analyses using RevMan 2011 and used the Grading of Recommendations, Assessment, Development, and Evaluations profiler to rate the quality of evidence of the primary outcomes. We analysed eight studies involving 1592 subjects. Meta-analysis of the RCTs showed that metformin had statistically significant effects on pregnancy-induced hypertension [PIH; risk ratio (RR) 0.54; 95% confidence interval (CI) 0.31, 0.91]. However, its effects on neonatal hypoglycaemia (RR 0.80; 95% CI 0.62, 1.02), rate of large-for-gestational age infants (RR 0.77; 95% CI 0.55, 1.08), respiratory distress syndrome (RR 1.26; 95% CI 0.67, 2.37), phototherapy (RR 0.94; 95% CI 0.67, 1.31) and perinatal death (RR 1.01; 95% CI 0.11, 9.53) were not significant. Our analyses suggest that there is no clinically relevant difference in efficacy or safety between metformin and insulin; however, metformin may be a good choice for GDM because of the lower risk of PIH. The advantages of metformin in terms of glycaemic control, PIH incidence and gestational age at birth are unclear, and should be verified in further trials.

Population pharmacokinetic study of cyclosporine in the hematopoietic stem cell transplant recipients.

OBJECTIVES: The aim of this study is to investigate the population pharmacokinetics (PopPK) of cyclosporine (CsA) in the Chinese hematopoietic stem cell transplantation (HSCT) recipients for promoting the individualization of CsA administration. METHODS: A total of 887 retrospective drug monitoring data points were collected from 58 HSCT recipients. Whole blood samples were collected at predose (C0) and 2 hours (C2) post dose. The administration of CsA was intermittent intravenous infusion, continuous intravenous infusion and oral. Population modeling was performed using the NONMEM (nonlinear mixedeffect modeling) program. A one compartment pharmacokinetic model was used to fit the data. RESULTS: Body surface area (BSA), administration route and postoperative days were identified as significant covariates for clearance (CL) according to the final model: CL = 31.0 × (BSA/1.59)0.761 × (ROUT) × (POD), where ROUT was 1.91 if the administration route was intravenous infusion, otherwise it is equal to 1. The POD was 0.818, 0.753, 0.539, and 0.509 for posttransplant Days 0 - 10, 11 - 20, 21 - 30 and more than 30 days, respectively. Administration route was a significant covariate for volume (V) according to the final model: V = 192 × (ROUT), where ROUT was 4.10, 3.63 and 1 when the administration route was continuous intravenous infusion, intermittent intravenous infusion and oral. The other covariates were not identified as a significant effect on CsA pharmacokinetic parameters. CONCLUSION: Body surface area, administration route and postoperative days should be considered in individual pharmacotherapy of cyclosporine for HSCT patient to achieve the desired therapeutic target.

[Cost-effectiveness of schistosomiasis comprehensive control in Lushan County from 2007 to 2012].

OBJECTIVE: To evaluate the cost-effectiveness of comprehensive control strategy which mainly controls the schistosomiasis infection source in Lushan County from 2007 to 2012. METHODS: The data of the schistosomiasis endemic, Oncomelania hupensis snail status, control technology, and funding were collected and analyzed statistically in the endemic villages of Lushan County from 2007 to 2012. RESULTS: The schistosome infection rate of the residents decreased from 0.04% in 2007 to 0 in 2012. The numbers of advanced schistosomiasis patients decreased from 128 in 2007 to 121 in 2012. No acute schistosomiasis patients were found. The average density of living snails decreased from 0.06 snial/0.1 m2 to 0.05 snail/0.1 m2, with the decreased rate of 16.67%, and no schistosome infected snails were found. However, the snail area increased from 15.84 hm2 in 2007 to 52.12 hm2 in 2012, with the rise rate of 229.04%. The year per capita was 200.48 yuan, the cost of the infection rate decreasing by 1% was 949,900 yuan, and the cost of living snail density decreasing by 1% was 5,698,200 yuan. CONCLUSION: The cost-effectiveness of comprehensive control strategy which mainly controls the schistosomiasis infection source is relatively good in Lushan County from 2007 to 2012.

Enhancement of fumaric acid production by Rhizopus oryzae using a two-stage dissolved oxygen control strategy.

Batch fermentative production of fumaric acid by Rhizopus oryzae ME-F12 was investigated in a 7-l stirred tank fermentor under different dissolved oxygen (DO) concentrations. High fumaric acid yield on glucose (0.56 g/g) was achieved under high DO concentration (80%), but the glucose consumption rate and fumaric acid productivity were rather low (0.91 and 0.51 g/l/h). Fumaric acid productivity was enhanced under low DO concentration (30%), but the fuamric acid yield on glucose decreased to 0.52 g/g. In order to achieve the high fumaric acid yield and productivity simultaneously, a two-stage dissolved oxygen control strategy was proposed, in which the DO concentration was controlled at 80% in the first 18 h and then switched to 30%. This was experimentally proven to be successful. Relatively high fumaric acid production (56.2 g/l), high fumaric acid yield on glucose (0.54 g/g), and high glucose consumption rate (1.3 g/l/h) were achieved by applying this strategy. The productivity (0.7 g/l/h) was improved by 37%, 21%, and 9%, respectively, compared with fermentations in which DO concentrations were kept constant at 80%, 60%, and 30%.

Two-stage analysis of pharmacokinetics of sufentanil administered by target-controlled infusion in Chinese patients.

BACKGROUND: Sufentanil is a suitable choice for target-controlled infusion (TCI) because of its shorter context-sensitive half-time. The current study was to estimate the pharmacokinetics of sufentanil TCI in Chinese patients using the two-stage analysis. METHODS: Twelve adult patients with American Society of Anesthesiologists (ASA) physical status I or II undergoing elective surgery under general anesthesia were included. Anesthesia was induced with propofol, rocuronium and sufentanil administered by TCI lasting for 30 minutes, with target effect-site concentration of sufentanil 4 or 6 ng/ml. Frequent arterial blood samples (1.5 ml) were taken during and up to 24 hours after sufentanil TCI. Before the end of surgery, another arterial blood sample (1.0 ml) was drawn for the blood-gas analysis. Plasma sufentanil concentrations were determined by liquid chromatography-tandem mass spectrometry (limit of quantitation was 5 pg/ml). The data were analyzed with the two-stage approach, linear regression and correlation analysis. RESULTS: The pharmacokinetics of sufentanil TCI were adequately described by a three-compartment model. The variables were derived as follows: the volume of central compartment (V(1)) was 5.4 L, volume of distribution at steady-state (Vdss) was 222.6 L, metabolic clearance (Cl(1)) was 0.84 L/min and elimination half-life (t(1/2Y)) was 389 minutes. Patients' age, gender and PaCO2 correlated significantly with the pharmacokinetic parameters. The Vdss, volume of slowly equilibrating compartment (V(3)) and t(1/2Y) increased, and rapid distribution clearance (Cl(2)) decreased with increasing patient age. Male patients had larger values of Vdss, volume of rapidly equilibrating compartment (V(2)) and V(3) than female patients. The Vdss and V(3) increased with higher PaCO2 values. There were no significant correlations between the pharmacokinetic variables and body weight, height, lean body mass, plasma albumin, sufentanil dose, duration of surgery, pH or base excess of blood (BE-B). CONCLUSIONS: The pharmacokinetics of sufentanil TCI in Chinese patients can be optimally described by a three-compartment model. The pharmacokinetic analysis technique may affect the pharmacokinetic parameters and correlations.

Pharmacokinetics of sufentanil administered by target-controlled infusion in Chinese surgical patients.

BACKGROUND: Target-controlled infusion (TCI) has been recently developed and successfully implemented in clinical practice. This study was conducted to determine the pharmacokinetics of TCI administered sufentanil in Chinese surgical patients. METHODS: The pharmacokinetics of sufentanil was investigated in 12 adult patients, aged 23-76 years, scheduled for prolonged surgery under general anesthesia. Anesthetic induction was carried out with propofol, rocuronium and TCI administered sufentanil aiming for target effect-site concentration of sufentanil 4 or 6 ng/ml. Sufentanil TCI lasted for 30 minutes. Frequent arterial blood samples (1.5 ml) were drawn during and up to 24 hours after sufentanil TCI. Plasma sufentanil concentrations were measured by liquid chromatography-tandem mass spectrometry; limit of sensitivity of mass spectrometry was 5 pg/ml. The data were analyzed with the nonlinear mixed-effect model program. RESULTS: The pharmacokinetics of TCI administered sufentanil were optimally described by a three-compartment model with the following parameters: the central volume of distribution (V(1))=5.4 L, the volume of distribution at steady-state (Vdss)=195.4 L, systemic clearance (Cl(1))=1.10 L/min, and elimination half-life (t(1/2) gamma)=271.8 minutes. Both age and gender affected the pharmacokinetic parameters. The rapid distribution clearance (Cl(2)) was negatively correlated with patient age, and the volume of slowly equilibrating compartment (V(3)) was positively correlated with age. The Cl(2) and the volume of rapidly equilibrating compartment (V(2)) were influenced by gender with male patients showing higher values of Cl(2) and V(2) than female patients. There was no relationship of body weight, lean body mass, plasma albumin, or target effect-site concentration of sufentanil with any of the pharmacokinetic parameters studied. CONCLUSIONS: The pharmacokinetics of TCI administered sufentanil in Chinese patients can be adequately described by a three-compartment model. Pharmacokinetics adjusted to the individual patient should improve the accuracy of TCI systems.

Clinical evaluation of target controlled infusion system for sufentanil administration.

BACKGROUND: Sufentanil target controlled infusion (TCI) provides stable analgesia, better hemodynamic control than a bolus injection of intravenous anesthetics, anticipated recovery and improved quality of anesthesia during perioperative period. This study evaluated the accuracy and feasibility of TCI system for sufentanil at high concentrations in Chinese surgical patients. METHODS: Twelve low risk adult patients undergoing elective surgery under general anesthesia were included in this study. Sufentanil was administered with a specific TCI system incorporating the population pharmacokinetic data of sufentanil previously reported, using a target effect-site concentration of sufentanil 4 or 6 ng/ml. Sufentanil TCI duration was 30 minutes. Frequent arterial blood samples were taken during and up to 24 hours after sufentanil TCI for determination of plasma sufentanil concentrations by liquid chromatography-mass spectrometry/mass spectrometry. The changes of circulatory system function during the procedure, recovery profile and adverse effects were recorded. Measured plasma sufentanil concentrations were compared with the values predicted by the TCI system. The bias (median performance error, MDPE), precision (median absolute performance error, MDAPE) and wobble (variability of performance error) of the sufentanil TCI system were determined. RESULTS: All patients had stable cardiovascular variables during induction and maintenance of anesthesia. Time to eye opening and extubation were (5.6 + or - 1.7) minutes when TCI set to 4 ng/ml and (7.2 + or - 2.3) minutes when set to 6 ng/ml. There was no episode of agitation, muscle rigidity or intraoperative awareness. The bias (MDPE), precision (MDAPE) and wobble of the sufentanil TCI system were -3.7%, 18.9% and 19.6% respectively during TCI, and the MDPE, MDAPE and wobble were -29.1%, 31.7% and 15.0% respectively after TCI (up to 8 hours). CONCLUSIONS: The TCI system programmed for sufentanil at 4 or 6 ng/ml was considered acceptable for clinical use in low risk Chinese surgical patients. But the relatively larger MDPE and MDAPE after TCI suggest improvements of the pharmacokinetic model are needed.