The clinical pharmacokinetics of ribavirin after a single oral dose of 600 mg ribavirin tablets in healthy Chinese volunteers was studied. A rapid and simple high performance liquid chromatography （HPLC） method was developed to determine the ribavirin concentration in human plasma. C18 column was used for separation with a column temperature of 25℃, the mobile phase was ultrapure water adjusted to pH 3 with acetic acid at the flow rate of 1 mL/min, and the detection wavelength was set at 207 rim. The linear range of the standard curves was 50.4-2016.0 ng/mL and the lower limit of quantification （LLOQ） was 50.4 ng/mL. The relative recoveries of ribavirin were more than 90% in plasma. The RSD of the intra-day precision was less than 10% and that of inter-day was less than 15%. The pharmacokinetic parameters of ribavirin were calculated by WinNonlin. Results indicated that the two-compartment model was a better model for describing the pharmacokinetics profile of ribavirin than one-compartment model. The AUC0-t was 10807.8 h.ng/mL, the CL/F was 64879.5 mL, and the Cmax was 525.1 ng/mL. These results provided the experimental data for the development of ribavirin dosage form.
Aim To evaluate liposome as an injectable delivery system of proteins, insulin was chosen as model drug and the hypoglycemic effect of PEG-coated liposomal insulin was tested.Methods The PEG-coated liposomal insulin was prepared by reversal-phase emulsion evaporation.For pharmacodynamic study, insulin (2.5 IU*kg-1) was intravenously administered in phosphated-buffered saline (PBS) solution, conventional liposomes, and PEG-coated liposomes, separately, to normal Wistar rats.Blood glucose levels were determined by the glucose oxidase method.Results The mean diameter of the PEG-coated liposomal insulin was 58.4 nm, while the encapsulation ratio reached 18.33%.After intravenous administration of insulin solution, insulin liposome, and PEG-coated liposomal insulin, the minimum blood glucose concentrations (Cmin %) reached 25.26±5.75%, 33.92±12.42%, and 42.39±10.5% of the initial level, respectively, and the time periods to reach the minimum blood glucose level (Tmin) were 0.7±0.3 h, 1.2±0.4 h, and 2.3±0.7 h, respectively.The relative pharmacological bioavailabilities of insulin liposome and PEG-coated liposomal insulin were 98.03% and 99.70%, respectively, compared with the control of insulin solution.Conclusion PEG-coated liposome can be developed as a relatively sustained injectable delivery system for insulin.Moreover, the liposome coated with PEG may have advantages over normal liposome.
