Establishing and improving the quality control system of drug clinical trial institutions is the key to ensure the quality of clinical trial. In recent years, the number of drug clinical trial has been continuously improved, and the quality control requirements have been continuously improved. However, in clinical work, the workload of medical staff is heavy, and the energy devoted to clinical trial is limited. Clinical research coordinator (CRC), as a participant and coordinator of clinical trial, has carried out transactional work related to non-medical judgment under the authorization and guidance of researchers, and has undertaken any specific work in clinical trial. Based on the quality control management experience of nosocomial CRC and hospital drug clinical trial institutions in West China Hospital of Sichuan University, this paper discusses the mode of nosocomial CRC participating in clinical trial quality control. By participating in the quality control of clinical trial, the nosocomial CRC has improved the quality control efficiency, enriched the quality control team and improved the overall level of CRC. This model enriches the quality control system of drug clinical trial.
Objective To describe pharmacokinetic of imatinib in a cohort of gastrointestinal stromal tumor (GIST) patients in routine clinical care from West China Hospital of Sichuan University. Methods The imatinib trough concentration (Cmin) in 42 patients with GIST who were taking imatinib in routine clinical care setting in West China Hospital from 2010 to 2016 was measured. The clinical features and follow-up data were collected. Results The mean imatinib Cmin in 42 patients was 1 757 μg/L (199–7 435 μg/L), 10 of 42 patients presented with Cmin values was lower than 1 000 μg/L. The imatinib Cmin of 18 patients received an imatinib dose of 300 mg/d or 24 patients treated with 400 mg/d imatinib was (1 313±479) μg/L and (1 775±1 520) μg/L, respectively (P=0.222), but the rate of low Cmin (lower than 1 000 μg/L) in the two different dose groups had no significant difference (P=0.347). In Cox regression, no statistically significant association between the low Cmin and the time to progression of GIST could be demonstrated 〔HR=0.171, 95%CI：(0.106, 12.990),P=0.898〕. Conclusion The preliminary results of limited cases in this study show that some GIST patients are systematically underexposed in routine clinical care, an individualized treatment based on monitoring of imatinib Cmin is likely to be more efficient than a fixed-dose treatment.
The pre-market approval and clinical application of innovative medical devices should be based on high-quality evidence, proving their reliability, safety and effectiveness. In 2016, the IDEAL (Idea, Development, Exploration, Assessment and Long-term follow-up) collaboration modified the original IDEAL framework and recommendation to the IDEAL-D methodological framework for the entire life cycle evaluation of innovative medical devices. The framework included five stages, namely the preclinical development stage, idea stage, exploration stage, assessment stage and long-term follow-up stage. This paper aims to interpret the study purpose, content and design at each step of the IDEAL-D framework based on IDEAL framework and recommendation (2019) to provide practical methodological guidance for the design and conduct of clinical research on innovative medical devices.
Objective To compare the systematic and lung pharmacokinetic parameters of moxifloxacin hydrochloride and explore a feasible tool to monitor drug concentration and evaluate therapeutic efficacy of respiratory fluoroquinolones. Methods Ten adult patients with community-acquired pneumonia or acute exacerbation of chronic bronchitis were enrolled.The subjects received a single dose of oral moxifloxacin hydrochloride 400 mg. Serum specimens were sampled at 0，1，2，3，4，8，24 h and sputum specimens were collected 0，1，2，4，8，20，24 h after administration，respectively.The serum and sputum concentrations of moxifloxacin hydrochloride were assayed by means of high-performance liquid chromatography. Standard pharmacokinetic parameters including peak concentrations(Cmax) and area under the concentration-time curve (AUC0-24 h) were assessed. Results Serum C(max) was（5.95±1.35）mg/L at 2 hours and serum AUC0-24 h was (58.72±8.11）mg·h-1·L-1 while sputum Cmax and AUC0-24 h were （16.18±6.47）mg/L at 3 hours and （138.04±78.29）mg·h-1·L-1 respectively，which were significantly higher than those in serum. Conclusion Oral administration of moxifloxacin hydrochloride to patients with respiratory infections results in rapid penetration into lung and maintain a one-fold drug concentration compared to blood concentration within 24 hours.Sputum drug concentration analysis demonstrates a superior pharmacokinetic profile of moxifloxacin in respiratory tract.
目的 研究高效液相色譜-質譜聯用法（HPLC-MS/MS）測定血漿中二亞油酰磷脂酰膽堿（DLPC）濃度測定的方法。 方法 2010年11月－2011年1月，7例受試者，3例服用多烯磷脂酰膽堿軟膠囊（試驗制劑），3例服用多烯磷脂酰膽堿膠囊（參比制劑），1例未服藥；采集服藥者血漿，對各種檢測方法、樣品預處理條件進行考核；用建立的方法對6例服藥者和1例未服藥者血漿DLPC濃度進行測定。 結果 最終建立的方法為：采用API 3000型HPLC-MS/MS液質聯用系統，多反應離子檢測模式，正離子掃描，大氣壓化學電離源，色譜柱為Ultimate CN分析柱（50.0 mm × 4.6 mm，5 ?m），流動相為甲醇︰水︰甲酸（80︰20︰0.05，V/V/V），流速為0.5 mL/min，格列齊特作為內標。受試者口服多烯磷脂酰膽堿軟膠囊試驗制劑與參比制劑后，DLPC血漿濃度水平均未見明顯的變化規律。未服藥者血漿DLPC濃度也有較高濃度水平。 結論 所建立的HPLC-MS/MS法，未能用于多烯磷脂酰膽堿軟膠囊生物等效性評價。
目的 采用高效液相色譜法測定受試者口服埃索美拉唑腸溶膠囊與埃索美拉唑鎂腸溶片后血藥濃度，評價埃索美拉唑腸溶膠囊的生物等效性。 方法 2009年9月－10月，36例健康男性受試者單次交叉口服埃索美拉唑腸溶膠囊（試驗制劑）和埃索美拉唑鎂腸溶片（參比制劑），測定給藥后不同時間點血漿中埃索美拉唑經時血藥濃度，采用DAS 2.0軟件進行藥物代謝動力學參數計算和生物等效性評價。 結果 受試者單次口服試驗制劑與參比制劑后，達峰時間分別為（2.19 ± 0.96）、（2.43 ± 0.92） h，峰濃度分別為（1 748.86 ± 615.81）、（1 442.92 ± 476.41） μg/L，藥時曲線下面積（AUC）0-t分別為（3 927.14 ± 1 839.10）、（3 878.79 ± 1 734.84） μg/L·h，AUC0-∞分別為（3 998.36 ± 1 866.22）、（3 918.31 ± 1 773.44） μg/L·h。試驗制劑與參比制劑的生物等效性為94.0%，其90%CI為（82.3%，107.2%）。 結論 埃索美拉唑腸溶膠囊與埃索美拉唑鎂腸溶片生物等效。
目的 采用高效液相色譜-質譜聯用法（HPLC-MS/MS）研究普羅布考片的人體藥物代謝動力學變化規律。 方法 2010年10月－11月，24例健康男性受試者單次口服普羅布考片0.5 g，采用HPLC-MS/MS法測定給藥后不同時間點血漿中普羅布考的經時血藥濃度，采用DAS 2.0軟件進行藥動學參數計算。 結果 受試者單次口服普羅布考片，達峰時間為（11.50 ± 6.66）h，峰濃度為（2 894.72 ± 1 320.53）ng/mL，藥-時曲線下面積（AUC）0-t為（238 876.96 ± 131 873.67） ng/mL· h，AUC0-∞為（259 989.08 ± 146 112.88）ng/mL· h，半衰期為（278.52 ± 164.72） h。結論 普羅布考片體內過程符合二室模型，單次口服具有較好的安全性。
目的 采用高效液相色譜-質譜聯用法研究鹽酸多奈哌齊口腔崩解片的人體藥物代謝動力學，并評價其生物等效性。 方法 2009年9月－11月對22例健康男性受試志愿者單次交叉口服鹽酸多奈哌齊口腔崩解片（試驗制劑）和鹽酸多奈哌齊普通片（參比制劑），測定給藥后不同時間點血漿中多奈哌齊經時血藥濃度，采用DAS 2.0軟件進行藥物代謝動力學參數計算和生物等效性評價。 結果 受試者單次口服試驗制劑與參比制劑后，達峰時間分別為（2.95 ± 1.16）、（3.19 ± 0.98） h，峰濃度分別為（9.98 ± 2.93）、（9.13 ± 2.05） ng/mL，藥時曲線下面積（0-t）分別為（470.76± 142.64）、（446.57 ± 137.30）ng/mL·h；藥時曲線下面積（0-∞）分別為（517.74 ± 169.79）、（489.47 ± 162.13）ng/mL·h。試驗制劑與參比制劑的生物等效性結果為104.7%，其90%置信區間為（98.4%，111.4%）。結論 鹽酸多奈哌齊口腔崩解片與普通片生物等效。