Pharmacokinetics and Adverse Reactions Assessment Among Different Dosage Forms of Mycophenolate Applied to Early Kidney Transplant Recipients / 中国药学杂志

OBJECTIVE: To evaluate the pharmacokinetic characteristics and adverse reactions among different dosage forms of mycophenolate applied to early kidney transplant recipients. METHODS: One hundred and twenty-one early kidney transplant recipients were divided into four groups, and received oral administration of mycophenolate mofetil capsules (Xiaoxi, MMF) (500, 750 and 1 000 mg, respectively), mycophenolate mofetil dispersible tablets (Saikeping, MMF-T) (500, 750 and 1 000 mg, respectively), mycophenolate mofetil dispersible tablets (Guoyaochuankang, MMF-DT) (500 and 750 mg, respectively), and mycophenolate sodium enteric-coated tablets (Mifu, EC-MPS) (360, 540, 720 and 900 mg, respectively) twice per day, respectively. The blood samples were collected on postoperative day 7 before and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 h after oral administration of different dosage forms of mycophenolate, respectively. Ultra high-performance liquid chromatography equipped diode array detector (UHPLC-DAD) was employed to determine the plasma concentration of MPA. Pharmacokinetic (PK) parameters of MPA were estimated by non-compartmental method using WinNoLin 6.3 software. RESULTS: There were no significant differences of mean ρ0 values (1 to 3 μg•mL-1) among four dose groups. The ρmax values were between 4 and 12 μg•mL-1, and their respective tmax values ranged from 1.0 to 3.0 h. Their t1/2 values were between 4 and 9 h. In addition, the AUC0-12 h values for MMF-T group were less than 30 μg•h•mL-1, while AUC0-12 h values for other three groups fall in the therapeutic window of MPA (30 to 60 μg•h•mL-1). Furthermore, power regression results indicated that dose proportionality of AUC0-12 h was nonlinear, and the correlation of AUC0-12 h and ρ0, ρmax were not conclusively linear (r=0.591 to 0.817, P<0.01) for MMF, MMF-T, MMF-DT and EC-MPS groups within 500-1 000 mg (bid), 500-1 000 mg (bid), 500-750 mg (bid) and 360-900 mg (bid), respectively. Moreover, moderate anemia, abnormal blood pressure and diarrhea mainly occurred in early kidney transplant recipients. When AUC0-12 h values of MPA were less than 30 μg•h•mL-1 or over 60 μg•h•mL-1, the patients were more likely to have various adverse reactions. CONCLUSION: PK parameters of MPA show marked individual difference among Chinese early kidney transplant recipients. There is a nonlinear relationship between drug dose and AUC0-12 h for MMF group (500-1 000 mg, bid), MMF-T (500-1 000 mg, bid), MMF-DT (500-750 mg, bid) and EC-MPS group (360-900 mg, bid), and their AUC0-12 h values are similar for different groups. There is inconclusively linear correlation between AUC0-12 h and ρ0, ρmax. There are few cases of adverse reactions in therapeutic window of MPA.

Dose-dependent Cardiac Dysfunction and Structural Damage in Rats after Shortwave Radiation / 生物医学与环境科学（英文）

Objective@#To detect the effects of shortwave radiation on dose-dependent cardiac structure and function in rats after radiation and to elucidate the mechanism of shortwave radiation induced cardiac injury to identify sensitive indicators and prophylactic treatment.@*Methods@#One hundred Wistar rats were either exposed to 27 MHz continuous shortwave at a power density of 5, 10, and 30 mW/cm for 6 min or undergone sham exposure for the control (the rats had to be placed in the exposure system with the same schedules as the exposed animals, but with an inactive antenna). The Ca , glutamic oxaloacetic transaminase (AST), creatine kinase (CK) and lactate dehydrogenase (LDH) content in the peripheral serum of the rats were detected by an automatic blood biochemical analyser. The electrocardiogram (ECG) of standard lead II was recorded by a multi-channel physiological recording and analysis system. The cardiac structure of rats was observed by light and electron microscopy.@*Results@#The results showed that the 5, 10, and 30 mW/cm shortwave radiation caused a significant increased in the levels of Ca , AST, CK, and LDH in the peripheral serum of rats. The cardiac structure was damaged by radiation and showed a disordered arrangement of myocardial fibres, the cavitation and swelling of myocardial mitochondria. These injuries were most significant 7 d after radiation and were not restored until 28 d after radiation.@*Conclusion@#Shortwave radiation of 5, 10, and 30 mW/cm can damage rat cardiac function, including damage to the tissue structure and ultrastructure, especially at the level of the myocardial fibres and mitochondria. Shortwave radiation at 5, 10, and 30 mW/cm induced damage to rat heart function and structure with a dose-effect relationship, i.e., the greater the radiation dose was, the more significant the damage was.

Dose dependence and durability of the therapeutic effects of Asparagus cochinchinensis fermented extract in an ovalbumin-challenged asthma model / 한국실험동물학회지

The butanol extract of Asparagus cochinchinensis roots fermented with Weissella cibaria (BAfW) significantly suppressed the inflammatory response induced by lipopolysaccharide (LPS) treatment in RAW264.7 cells. To investigate the dose dependence and durability of BAfW on the anti-asthma effects, alterations in key parameters were measured in ovalbumin (OVA)-challenged Balb/c mice treated with the different doses of BAfW at three different time points. The number of immune cells, OVA-specific IgE level, thickness of respiratory epithelium and mucus score decreased significantly in a dose-dependent manner in response to treatment with 125 to 500 mg/kg BAfW (P < 0.05), although the highest level was detected in the 500 mg/kg treated group. Moreover, the decrease in these parameters was maintained from 24 to 48 h in the 500 mg/kg of BAfW treated group. At 72 h, the effects of BAfW on the number of immune cells, OVA-specific IgE level and thickness of respiratory epithelium partially disappeared. Overall, this study provides the first evidence that the anti-asthma effect of BAfW may reach the maximum level in OVA-challenged Balb/c mice treated with 500 mg/kg and that these effects can last for 48 h.