Objective To evaluate the legitimate of regional artery infusion chemotherapy in the treatment of gastric carcinoma. MethodsThe pharmacokinetics of 5-Fu after different route of administration was studied. Results High concentration of 5-Fu found in portal vein via left-gastric intra-artetial administration were 4-40 folds higher than the group via intravenous administration.The time of high concentrations of 5-Fu via left-gastric intra-arterial administration maintained significantly longer than by intravenous administraion. The concentration of 5-Fu in tumor tissues and paratumorous lymph tissues by intra-arterial administration were 19 times and 23 times of the group by intravenous administration. Conclusion Regional arterial infusion chemotherapy can significantly increase the concentration of chemotherapeutic drugs in the tumorous region.
OBJECTIVE To study the character of cefazolin (CEZ) pharmacokinetics on Neijiang pig and human. METHODS The serum concentration of CEZ in 8 normal Chinese adult men, 9 of 8-month male Neijiang pigs and 5 of 4-month male Neijiang pigs were detected by high-performance liquid chromatography (HPLC). RESULTS The pharmacokinetic parameters suggested that two-compartment model was found in all groups after intramuscular injection of CEZ. In normal men, 8-month pigs and 4-month pigs, the peak time (Tmax) was (58.8 +/- 13.0), (19.7 +/- 9.9) and (18.2 +/- 8.6) min respectively, T1/2 alpha was (42.3 +/- 19.7), (19.0 +/- 7.7) and (9.3 +/- 1.9) min, the peak concentration (Cmax) was (101.6 +/- 14.6), (28.7 +/- 9.0) and (23.5 +/- 4.6) mg/L; Vd was (0.096 +/- 0.016), (0.374 +/- 0.184) and (0.386 +/- 0.211) L/kg; T1/2ka was (22.5 +/- 6.8), (8.6 +/- 4.8) and (10.6 +/- 10.2) min; T1/2 beta was (117.3 +/- 8.6), (84.2 +/- 9.8) and (45.1 +/- 11.5) min; clean rate of plasma Cl was (0.8 +/- 0.1), (6.8 +/- 1.2) and (11.0 +/- 3.0) ml/kg.min; AUC was (21,803 +/- 4,145), (2,407 +/- 443) and (1,636 +/- 685) mg.min/L. CONCLUSION It could conclude that the Neijiang pigs could eliminate CEZ effectively, but the absorption, distribution and elimination of CEZ in pigs were quicker than that of in human while the absorption from muscle in both pig groups were lower than that in human.
ObjectiveTo study the pharmacokinetics of lovastatin/niacin sustained-release tablets in healthy Chinese volunteers. MethodsEligible subjects were enrolled to receive a single dose of 20/500, 20/750 and 20/1 000 mg lovastatin/niacin sustained-release tablets and multiple dose of 20/1 000 mg lovastatin/niacin sustainedrelease tablets, one time per day, sustained for 5 days, respectively. Blood samples were obtained before dosing and up to 10, 20, 30, and 45 minutes, and 1 hour, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, and 15 hours after dosing. Niacin, niacinamide, nicotinuric acid and lovastatin were detected by high performance liquid chromatography-tandem mass spectrometry method. ResultsThe peak concertration and the area under the plasma concentration-time curve (0-t) of nicotinuric acid had linear dynamics characteristics with the dosage when the dose of niacin was between 500 and 1 000 mg. After multiple dosing, pharmacokinetics parameters of nicotinuric acid and lovastatin were close. No significant diTherence was found between male and female subjects. ConclusionLovastatin/niacin sustained-release tablets possess linear kinetics. Accumulation is not significant after multiple dosing. Gender doesn't affect the pharmacokinetics parameters.
Objectives To explore intraocular drug concentration changes and the pharmacokinetics after topically applied of bevacizumab with annexin A5-associated liposome on rabbit eyes. Methods A total of 105 healthy New Zealand white rabbits were selected and divided randomly into 3 groups (group A, B and C), and each group had 35 rats. Bevacizumab with annexin A5-associated liposome, bevacizumab liposome and bevacizumab were topically applied 50 μl respectively on right eyes of rabbits in group A, B and C, respectively. Aqueous, vitreous body and retina/choroid were obtained at 5, 15, 30 minutes and 1, 2, 4, 8 hours and the free bevacizumab concentrations in these ocular tissues were measured by ELISA (enzyme linked immunosorbent assay). DAS 2.1.1 software was used to fit the pharmacokinetic parameters. Results The peak drug concentrations in aqueous humor of the eyes in group A, B, C were at 15 minutes after topical administration and the difference was statistically significant (F=301.061,P＜0.01). The peak drug concentrations in vitreous of the eyes in the group A, B, C were at 2 hours after topical administration and the difference was statistically significant (F=885.997,P＜0.01). The peak drug concentrations in retina/choroid of the eyes in the group A, B, C were at 1 hour after topical administration and the difference was statistically significant (F=644.908,P＜0.01). Least significant difference pair-wise test found that the drug concentrations in aqueous humor, vitreous and retina/choroid of group A was higher than that of the group B and C respectively (P＜0.05), while that of the group B and C had no significant different (P＞0.05). Pharmacokinetic fitting analysis found that the half-life (t½) of bevacizumab in aqueous humor were 1.14, 1.29, 1.29 hours, the distribution t½ were 1.40, 1.50, 1.42 hours and the eliminated t½ were 2.62, 2.84, 2.73 hours in vitreous, the distribution t½ were 2.61, 2.99, 2.70 hours and the eliminated t½ were 2.61, 2.99, 2.70 hours in retina/choroid respectively for the 3 groups. Changes of bevacizumab concentration in aqueous humor of rabbit eyes for 3 groups was complied with one compartment model, and that in vitreous body and retina/choroid complied with two compartment model. Conclusions Topically applied annexin A5-associated liposome has higher ocular concentrations of bevacizumab than those of controls. Changes of bevacizumab concentration in aqueous humor of rabbit eyes was complied with one compartment model, and that in vitreous body and retina/choroid complied with two compartment model.