ABSTRACT
Objective To evaluate the pharmacokinetics, drug concentration and effect relationship of PEGylated IL-11 mutein (PEG-mIL11) in cynomolgus monkeys through the validated anti-PEG-ELISA method. Methods PEG-mIL11 at 350 μg/kg was subcutaneously injected in cynomolgus monkeys, and the blood samples were collected at various time points. An anti-PEG-ELISA method was validated and used to investigate the concentration of PEG-mIL11, and platelet counts were measured to explore the relationship of drug concentration and effect. Results Results of the validation test demonstrated that PEG-mIL11 in monkey blood could be quantitated by anti-PEG-ELISA. Its linear range was (26.34-200) ng/ml. The specificity, accuracy and precision of the method met the present criteria. The terminal elimination half-life (T1/2) of PEG-mIL11 was (13.4 ± 2.4) h, the peak time (Tmax) was (6.7 ± 2.3) h, the peak concentration (Cmax) was (2.4 ± 0.5) μg/ml, the area under curve (AUC)(0-t) was (77.7 ± 15.6) μg∙h/ml, and the clearance (CL) was (4.6 ± 0.8) ml/ (h·kg). The thrombopoietic effect did not relate directly with the concentration of PEG-mIL11 in serum. Conclusion Anti-PEG-ELISA, used in this study to measure the concentration of PEG-mIL11, is a steady, reliable and specific method for PEGmIL11 pharmacokinetic study, and its chemical modification by PEG possesses long circulating half-lives, thereby suggesting less frequency of administration.
ABSTRACT
AIM: To establish a sensitive HPLC method for determining the concentrations of paeonol in human plasma and to evaluate its pharmacokinetic characteristics. METHODS: A single oral dose of 160 mg paeonol capsules was given to 24 Chinese healthy volunteers. Paeonol was separated on a XB-C18 column with tetrahydrofuran-methanol-water-phosphonic acid (6∶60∶34∶0.1, V∶V) as mobile phase. The plasma concentrations of paeonol were determined and its pharmacokinetic parameters were calculated and evaluated using DAS 2.0. RESULTS: The linear range of the paeonol was 10-500 ng/mL and the determination limit was 10 ng/mL. The main pharmacokinetic parameters, as Cmax, tmax, t1/2,AUC0-3, AUC0-∞ after a single dose of paeonol capsules were (116±46)ng/mL,(1.02±0.13) h,(1.03±0.35) h, (174±45) ng/mL, (217±56) ng/mL,respectively. CONCLUSION: The HPLC method for determining paeonol concentration in plasma is rapid, sensitive and suitable for pharmacokinetic studies.