Quinacrine不同给药途径对家兔血药浓度的影响

目的 研究 quinacrine经不同途径给药的血药浓度 ,了解 quinacrine经阴道向子宫内给药绝育 (quinacrine女性非外科绝育法 )可能产生的毒副反应。方法 以兔为模拟对象 ,用荧光分析法分别测定宫腔内缓释给药、静脉、口服和输卵管内注射等 4种不同途径给quinacrine的血药浓度变化。结果 血药浓度峰值以静脉给药法最高 ,宫腔内缓释给药法最低。宫腔内缓释给药法的血药浓度水平接近其他给药方法血药浓度水平的残余浓度。血药浓度下降的起点静脉法在给药后立即产生 ,口服法在给药后 8h出现 ,输卵管内注射法见于给药后 4h ,而宫内缓释法则可维持到 7d。结论 从是否产生全身性的毒副反应的角度看 ,quinacrine宫腔内缓释给药法比口服法低 。

Preparation of anti-resistant stealthy liposomes by incorporating vincristine with quinacrine and the pharmacokinetics in Sprague-Dawley rats

Aim The objectives of the present study were to prepare stealthy vincristine plus quinacrine liposomes and evaluate the pharmacokinetics in Sprague-Dawley rats. Methods Anti-resistant stealthy liposomes were prepared by incorporating vincristine with quinacrine together using the ammonium sulfate gradient loading procedure. For the pharmacokinetic study, Sprague-Dawley rats were divided into two groups： each rat in the Group Ⅰwas administered intravenously via tail vein as stealthy liposomal vincristine plus quinacrine, and the Group Ⅱ similarly given as a mixture solution of free vincristine plus free quinacrine. The concentrations of vincristine and quinacrine in plasma were measured by HPLC with diode array detection and fluorescence detection, respectively. Results The mean particle size of stealthy liposomes was 135.9 ±7.1 nm and the encapsulation efficiencies of stealthy liposomes were 〉 90% for vincristine, and 〉 85% for quinacrine, respectively. Administered as the stealthy vincristine plus quinacrine liposomes, the plasma exposures of both vincristine and quinacrine were significantly extended, and the mean concentrations of both vincristine and quinacrine were significantly higher compared to those given as the mixture solution of free vincristine plus free quinacrine. The Cmax, t1/2, AUC0-24 h values of vincristine for stealthy liposomal group were significantly increased, but the total clearance Cl values decreased, as compared to those of free drug group, respectively. Similarly, the Cmax, t1/2 and AUC0-24 h values of quinacrine for the stealthy liposomal group were significantly increased, but the total clearance C1 values decreased, as compared to those of free quinacrine. Conclusion The anti-resistant stealthy liposomes are successfully prepared by incorporating vincristine with quinacrine, and the liposomes extend significantly the duration in blood circulation and improve evidently the plasma concentrations of both vincristine and quinacrine.

Retrospective study on the efficacy and safety of quinacrine sterilization

Aim: To observe the efficacy and safety of quinacrine sterilization.Methods: This retrospective study was to evaluate the efficacy and safetyof quinacrine sterilization in 572 cases in Jiangsu and Guizhou Provincesfrom 1993 to 1997. A total of 588 cases of surgical sterilization performed atthe same time served as the controls. Results: Two groups had similardemographic and gynecological characteristics. The multiple decrement lifetable analysis showed that the 12th month gross cumulative failure rate forquinacrine sterilization was 3.13% . Serious side effects occurred in 2 cases(0.35%); one is ectopic pregnancy (20 months after treatment) and theother, allergy reaction (10 minutes after the second insertion). The liverand renal functions were all normal in both groups. No cance cells/suspect-ed cancer cells were found. In the quinacrine group, the acceptability was99.6% . Conclusions: The quinacrine method has a high acceptability,but the efficacy is relatively low. It is a safe method of contraception inshort-term study, while the long-term safety warrants further investigation.

Quinacrine pretreatment reduces microwave-induced neuronal damage by stabilizing the cell membrane

Quinacrine, widely used to treat parasitic diseases, binds to cell membranes. We previously found that quinacrine pretreatment reduced microwave radiation damage in rat hippocampal neurons, but the molecular mechanism remains poorly understood. Considering the thermal effects of microwave radiation and the protective effects of quinacrine on heat damage in cells, we hypothesized that quinacrine would prevent microwave radiation damage to cells in a mechanism associated with cell membrane stability. To test this, we used retinoic acid to induce PC12 cells to differentiate into neuron-like cells. We then pretreated the neurons with quinacrine （20 and 40 mM） and irradiated them with 50 mW/cm^2 microwaves for 3 or 6 hours. Flow cytometry, atomic force microscopy and western blot assays revealed that irradiated cells pretreated with quinacrine showed markedly less apoptosis, necrosis, and membrane damage, and greater expression of heat shock protein 70, than cells exposed to microwave irradiation alone. These results suggest that quinacrine stabilizes the neuronal membrane structure by upregulating the expression of heat shock protein 70, thus reducing neuronal injury caused by microwave radiation.

Randomized clinical study of five days apostrophe therapy with mebendazole compared to quinacrine in the treatment of symptomatic giardiasis in children

AIM： To compare the efficacy and safety of five days apostrophe therapy of mebendazole （MBZ） versus quinacrine （QC） on human giardiasis in children.METHODS： A clinical trial was carried out in paediatric patients （aged 5-15 years） with confirmed symptomatic G. duodenalis mono-infection. Patients were randomly assigned to receive either MBZ [200 mg taken three times per day GRID） （n = 61）] or QC [2 mg/kg bodyweight tid （n = 61）], both for five days. Follow-up faecal samples were obtained at 3, 5 and 7 d after the end of the treatment.RESULTS： Although the frequency of cure was higher for QC （83.6%） than for MBZ （78.7%）, the difference was not statistically significant （P 〉 0.05）. Adverse events were reported more in the QC group （P 〈 0.05）, all of them transient and self-limiting.CONCLUSION： Despite final cure rates ocurring lower than expected, the overall results of this study reconfirmed the efficacy of MBZ in giardiasis and also indicate that, although comparable to QC, at least in this setting the 5 d course of MBZ did not appear to improve the cure rates in this intestinal parasitic infection.

Retrospective Study on the Efficacy and Safety of Quinacrine Sterilization

Objective To observe and evaluate the efficacy and safety of quinacrine sterilization Methods A total of 572 cases of quinacrine sterilization preformed during the 4 years from 1993 to 1997 in Jiangsu and Guizhou Provinces were employed in this study. The efficacy and safety of quinacrine sterilization in those case were studied and evaluated, with 588 cases of surgical sterilization performed at the same time being the control group. Results Both groups were with identical demographic and gynecological characteristics. The result of multiple decrement life table analysis showed the 12th gross cumulative failure rates for quinacrine sterilization was 3.13% and serious side effects occurred in only 2 cases accounting for 0.35%. One was ectopic pregnancy (20 months after treatment).The other was due to anaphylaxis in 10 minutes after the second insertion). No difference in the liver and nephic functions was detected and no suspected cancer cells or cancer cells were found in the two groups. 99.6% of the 572 women interviewed accepted the quinacrine sterilization. Conclusions Quinacrine sterilization method is with high acceptability but comparatively low effectiveness. It has been proved to be a safe method of contraception in short term. However, the safety of long term still needs further study.