Objective To evaluate the safety and tolerance of medicinal charcoal enteric-coated tablets in healthy volunteers. Methods A total of 44 healthy volunteers were randomly divided into 6 single-dose groups (0.5 g, 2 g, 4 g, 6 g, 8 g and 10 g) and a multiple-dose group (3 g, 3 times a day, for 14 days). The safety profile and tolerance were evaluated by observing symptoms, vital signs, and laboratory tests. Results No serious adverse event was reported for any volunteer. Abdominal distension occurred in 2 volunteers in the 4 g dose group and the 6 g dose group. One volunteer in the 8 g dose group experienced nausea and vomiting. Transient decrease in white blood cell count was observed in one volunteer in the 10 g dose group. Abdominal distension occurred in 2 volunteers of the multiple-dose group. Conclusion Based on our findings, the maximum tolerated dose of medicinal charcoal enteric-coated tablets in Chinese healthy volunteers is 10 g. The recommended dose for subsequent clinical trials is 3 g, 3 times a day.
The teaching of Clinical Pharmacology plays a very important role in medical education. In this article, we introduce our exploration and practice in Clinical Pharmacology course in West China Hospital of Sichuan University, which combines Good Clinical Practice with teaching methods such as problem-based learning and case-based learning. Furthermore, we analyze the actual effects in optimizing teaching content, renewing teaching mode, and improving teachers’ teaching ability, etc. We hope this article could provide new ideas for the teaching reform of undergraduate Clinical Pharmacology course.
Objective To investigate the pharmacokinetic profiles and safety of clevidipine butyrate injectable emulsion in Chinese healthy subjects, following intravenous administration with gradually increasing doses. Methods From June to July 2020, 12 Chinese healthy adult subjects were enrolled in the single-center, single-arm, open-label clinical trial. The gradually increasing doses were 1, 2, 4 and 6 mg/h, starting with the initial infusion rate of 1 mg/h. Each dose was infused for 2 min before increasing to the next dose. After reaching 6 mg/h, the infusion rate was maintained for 20 min. Plasma concentrations of clevidipine and its metabolite H152/81 were detected using high performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were calculated by non-compartmental analysis using WinNonlin 8.0. Data following a normal distribution were presented as mean ± standard deviation, while data following a log-normal distribution were presented as geometric mean ×/÷ geometric standard deviation. Results Pharmacokinetic parameters of clevidipine were as follows: elimination half-life (t1/2) (3.79×/÷2.35) min, peak concentration (Cmax) (11.71±3.79) ng/mL, area under concentration-time curve from time 0 to the last measurable concentration (AUC0–t) (222.89±61.79) min·ng/mL, area under concentration-time curve from time 0 extrapolated to infinite time (AUC0–∞) (233.35±78.64) min·ng/mL, and median time to peak concentration (Tmax) 18.00 min. Pharmacokinetic parameters of H152/81 were as follows: t1/2 (194.68×/÷1.42) min, Cmax (162.00±23.35) ng/mL, AUC0–t (12794.40±1976.56) min·ng/mL, AUC0–∞ (41215.86±10110.90) min·ng/mL, and median Tmax 31.00 min. Following the administration, clevidipine rapidly affected heart rate and blood pressure. The heart rates of subjects increased slightly, and the decrease in diastolic blood pressure was greater than that in systolic blood pressure. The effects disappeared within 4 min after the infusion ended. Only 1 mild adverse event was reported. Conclusion Clevidipine shows a short half-life, as well as good safety and tolerability in Chinese healthy subjects.
Objective To evaluate the safety and tolerance of pegfilgrastin (PEG-G-CSF) in Chinese healthy volunteers. Methods Thirty healthy volunteers were randomly divided into five single-dose groups to receive PEG-G-CSF 15, 30, 50, 60 or 75μg/kg by hypodermic injection. The safety profile and tolerability were evaluated by observing symptoms, vital signs, laboratory tests and electro cardiogram. Results No serious adverse event was reported for any volunteer. Transient dizziness occurred in one person in the 50 μg/kg dose group, and mild dizziness and ostalgia was found in all six people in the 75μg/kg dose group, of whom one experienced transient fever and two experienced mild diarrhea. No clinically significant changes in laboratory tests and electrocardiogram were found during the follow-up period. Conclusions The maximum tolerated dose of PEG-G-CSF injection in Chinese healthy volunteers is 60 μg/kg. Doses below 60μg/kg can be well tolerated. The recommended dose for phase II clinical trials is 60 μg/kgone, one dose for each cycle of chemotherapy.
Objective To assess the tolerability and safety of Yinhuang injection in Chinese healthy volunteers. Methods Thirty-two healthy subjects were enrolled in the single-dose study. Each subject was administered one of the seven doses of 40, 120, 240, 320, 400, 480, and 560 mg, respectively, by intravenous injection. The sample sizes were 2, 4, 6, 6, 6, 4 and 4, respectively, for each dose group. Twelve healthy subjects were enrolled in the multi-dose study. The subjects in the lower dose group were administered 240 mg and the subjects in the higher dose group were administered 400 mg Yinhuang by intravenous injection once a day for consecutive 7 days. The sample sizes for both groups were 6. The safety was evaluated based on clinical symptoms, vital signs, physical examinations, electrocardiogram (ECG), laboratory tests and adverse events. All analyses were performed by using the software package SAS version 9.1. T-test and analysis of variance were used for continuous variables. Chi-square test and Fisher’s exact test were used for categorical variables.Results A total of 44 healthy volunteers completed the tolerance test. No serious adverse event and clinically significant changes in vital signs, ECG and laboratory tests were found in both single-dose groups and multi-dose groups. Among two mild adverse events, dizziness occurred in one subject in 480 mg dose group in the single-dose trial, which was probably related to the experimental drug. Conclusion Yinhuang injection is safe and well-tolerated in Chinese healthy subjects after administration of single-doses (40-560 mg) and multi-doses (240-400 mg once a day for consecutive 7 days). The maximum-tolerated dose of Yinhuang injection is at 560 mg in the single-dose trial. The dose regimen of 240-400 mg a day is recommended for phase II study.
【摘要】 目的 評價麻敏維C緩釋膠囊（每粒含鹽酸偽麻黃堿90 mg和馬來酸氯苯那敏4 mg）在人體的生物等效性。 方法 于2006年6月采用隨機交叉自身前后對照試驗設計，26例受試者分別單次和多次空腹口服麻敏維C緩釋膠囊（試驗制劑）和復方鹽酸偽麻黃堿緩釋膠囊（參比制劑），與不同時間點取血樣，采用液-質聯用（HPLC/MS）法測定人血漿中鹽酸偽麻黃堿和馬來酸氯苯那敏的濃度，以DAS軟件計算藥物代謝動力學參數，并進行生物等效性評價。 結果 單次給藥后，兩組分的主要藥物代謝動力學參數無統計學意義（Pgt;0.05）。試驗制劑中馬來酸氯苯那敏和鹽酸偽麻黃堿生物利用度分別為104.31%和109.19%。多次給藥后，兩組分的主要藥物代謝動力學參數無統計學意義（Pgt;0.05）。試驗制劑的馬來酸氯苯那敏和鹽酸偽麻黃堿的生物利用度分別為103.58%和99.37%。 結論 麻敏維C緩釋膠囊和復方鹽酸偽麻黃堿緩釋膠囊具有生物等效性。【Abstract】 Objective To investigate the bioequivalence of delayed-release capsule of ephedrine-chlorphenamine-vitamin C. Methods In June 2006, 26 healthy volunteers were administrated with delayed-release capsule of ephedrine-chlorphenamine-vitamin C or delayed-release capsule of ephedrine-chlorphenamine in a randomized and two-way crossover design with single or multiple dosage. The plasma concentrations were determined by HPLC/MS method. The pharmacokinetic parameters and bioequivalence were calculated by DAS software. Results After single dose administration, no significant differences were found in tmax, Cmax, t1/2, and AUC0-t between the two preparations. The relative bioavailability of the test preparation was 104.31% in chlorphenamine and 109.19% in ephedrine, respectively. After multiple dose administration, no significant differences were found in tmax, Cmax, t1/2, and AUC0-t between the two preparations. The relative bioavailability of the test preparation was 103.58% in chlorphenamine and 99.37% in ephedrine, respectively. Conclusion Delayed-release capsule of ephedrine-chlophenamine-vitamin C is equivalent to the reference preparation.