A preliminary study of pharmacokinetics of evodiamine hydroxypropyl-β-cyclodextrin inclusion complex / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare the pharmacokinetic parameters of evodiamine hydroxypropyl-β-cyclodextrin inclusion complex and free evodiamine suspension in rats, and investigate the pharmacokinetic characteristics of evodiamine inclusion complex.</p><p><b>METHODS</b>Both water solubility and cumulative release percentage of EHD were tested with evodiamine as the control. Blood samples were collected from the venous plexus of SD rats after intravenous administration with evodiamine inclusion complex and free evodiamine at 100 mg/kg (equivalent evodiamine dose). Plasma concentrations of evodiamine were determined by high-performance liquid chromatography (HPLC), and the pharmacokinetic parameters were calculated using DAS 2.1.1.</p><p><b>RESULTS</b>The evodiamine inclusion complex showed a better water solubility (18.46±0.36 µg/mL) and a higher cumulative release percentage [(76.8±4.9)%] than free evodiamine. The pharmacokinetic parameters of evodiamine inclusion complex and free evodiamine in rats were as follows: Cmax, 252.5±12.43 vs 161.3±3.45 µg/L; T(max), 4.00±0 vs 4.07±0 h; MRT(0-∞), 8.46±0.91 vs 4.43±0.74 h; AUC(0-t), 2266.40±28.64 vs 911.92±8.53 µg·L(-1)·h(-1); AUC(0-∞), 2359.76±31.58 vs 919.16±9.73 µg·L(-1)·h(-1). The relative bioavailability of evodiamine inclusion complex was 256.73%.</p><p><b>CONCLUSION</b>Compared with free evodiamine, evodiamine inclusion complex has a higher bioavailability.</p>

Pharmacokinetics and bioequivalence of evodiamine novel nano emulsion in rats / 第二军医大学学报

Objective To establish an HPLC approach for determining the plasma drug concentration of evodiamine (EVO) in evodiamine novel nano emulsion (ENNE) in rats, and to investigate the pharmacokinetics and bioequivalence of ENNE in rats. Methods Twelve SD rats were evenly randomized into two groups andwere administered intragastrically with ENNE (containing EVO 100mg/kg) or EVO (100mg/kg). The plasma drug concentrations of EVO were measured at 5min,min, 15 min, 30 min, 45 min, 1 h, 2 h, 5 h, 8 h, 12 h, 24 h, 48 h and 72 h after administration of ENNE or EVO by HPLC. The chromatographic conditions were as following: the mobile phase was methanol and 0.1% of formic acid-water solution (66: 34, V/V), the flow rate was 1 mL/min, the injection volume was 100 μL, and the detection wavelength was 225 nm. The concentration-time curve was drawn by excel software, and the main pharmacokinetic parameters and bioequivalence were calculated by DAS 2. 1. 1 software. Results The established method was fast, accurate, and had good linear correlation. The AUCo-∞ of ENNE and EVO were (8 248. 88 ± 69. 92) μg • h • L-1 and (884. 82 ± 83. 52) μg • h • L-1, and the t1/2 of ENNE and EVO were (1. 70 ± 0. 60) h and (1. 05 ± 0. 45) h, respectively. The AUCo-∞ of ENNE was 9 times that of EVO, and the t1/2 of ENNE was 1. 62 times that of EVO. ENNE and EVO were not bioequivalent. Conclusion Bioavailability and absorption of ENNE are higher than EVO, and ENNE and EVO are not bioequivalent.

Pharmacokinetics of neostigmine bromide multivesicular liposomes in rats / 第二军医大学学报

Objective To study the pharmacokinetics of neostigmine bromide multivesicular liposomes (NB-MVLs) and conventional neostigmine bromide (NB) injection in rats. Methods Twelve healthy rats, half male and half female, were randomly divided into two groups. One group was injected with NB-MVLs and the other with reference NB (0.15 mg/kg). RP-HPLC was used to examine neostigmine concentrations in rat plasma at different time points, and the pharmacokinetic parameters and relative bio-availability were calculated. Results Pharmacokinetic parameters of NB-MVLs and NB were as follows: AUC0-t (35.56±4.62) mg·h·L-1 vs (15.97±5.22) mg·h·L-1;Tmax(2.40±0.89) h vs (0.45±0.11) h; Cmax (2.49±0.31) mg/L vs (4.61±0.91) mg/L; and t1/2 (15.14± 6.81) h vs (1.79±0.27) h, respectively. AUC0-t, AUC0-∞ and Cmax were studied by DAS 2.1.1 software for double unilateral t test and [1-2α] 90% confidence interval, and Tmax was precessed by Wilcoxon nonparametric test to evaluate the bioequivalence of NB-MVLs and NB. The result showed that NB-MVLs and NB were not bioequivalent. Conclusion Neostigmine in the form of multivesicular liposomes has improved bioavailability and stable drug release; NB-MVLs and NB are not bioequivalent.