Comparative pharmacokinetic (PK) analysis is often carried out throughout the entire period of drug development, the common approach for the assessment of pharmacokinetics between different treatments requires that the individual PK parameters, which employs estimation of 90% confidence intervals for the ratio of average parameters, such as AUC and Cmax, these 90% confidence intervals then need to be compared with the pre-specified equivalent interval, and last we determine whether the two treatments are equivalent. Unfortunately in many clinical circumstances, some or even all of the individuals can only be sparsely sampled, making the individual evaluation difficult by the conventional non-compartmental analysis. In such cases, nonlinear mixed effect model (NONMEM) could be applied to analyze the sparse data. In this article, we simulated a sparsely sampling design trial based on the dense sampling data from a truly comparative PK study. The sparse data were analyzed with NONMEM method, and the original dense data were analyzed with non-compartment analysis. Although the trial design and analysis methods are different, the 90% confidence intervals for the ratio of PK parameters based on 1000 Bootstrap are very similar, indicated that the analysis based on NONMEM is a reliable method to treat with the sparse data in the comparative pharmacokinetic study.

The paper aimed to find the optimal combination and evaluation of the interactions of antitumor effect of the curcumin (Cur) and adriamycin (ADM) in vitro. According to the factorial design and data characteristics, the parameter method combined with the response surface approach were used to analyze the pharmacodynamic interactions of in vitro antitumor effects of the combination of Cur and ADM at different dosages. The results showed that the dose-effect relationship of the combination with the ratio of ADM-Cur 1:3 showed significant differences in comparison with either used alone. The dose-effect curve was shift left in combination. The combination of adriamycin (ADM, 0.693-2.132 micromol L(-1)) and curcumin (Cur, 2.047-6.304 micromol L(-1)) with a fixed ratio (1:3) showed a synergism. With increasing doses of the combination, there is an additive effect. Computer simulation showed a trend of decreasing difference between the observed and expected effects with the dose increasing in Cur from 6.304 to 16.0 micromol L(-1) and ADM from 2.132 to 5.3 micromol L(-1). The response surface analysis showed the optimal combination to be Cur 18.50 micromol L(-1) and ADM 3.89 micromol L(-1) with a ratio of 5:1. This study suggests that the parameter method combined with the response surface analysis provides richer and more reasonable information, and is helpful for quantitative design of drug combination therapy and to describe the nature and degree of drug interaction.

Objective To investigate the efficacy and safety of radiofrequency ablation (RFA) combined with transarterial chemoembolization (TACE) for treating of hepatic metastasis. Methods From Mar. 2005 to Oct. 2010, 22 males and 14 females with hepatic metastasis were enrolled in this study. Mean age of the patients was 63±12 (42-82) years. Tumor size was (4.5±2.4) cm (min.1.5 cm, max. 12.0 cm). Totally 47 lesions were treated with single metastasis in 29 cases and multiple ones in 7 cases. All cases were failed to chemotherapy or could not stand for the side effect of chemotherapy. Contrast enhanced CT scan was given to all patients before RFA+TACE. For lesions with rich blood supply, TACE was given and then RFA. For those with poor blood supply, RFA was given first and then TACE. For multiple lesions, RFA+TACE was given one by one for each lesion. As for follow up, ultrasound and blood check was given monthly. Enhanced CT scan was given every 3 month. For residual lesions or recurrent lesions, RFA+TACE were given repeatedly. The whole patients was divided into two groups according to the image follow up including complete ablation group and partial ablation group. For complete ablation group, no further treatment was given. For partial ablation group, if it was not suitable for further RFA, repeated TACE was given there after. The end point of follow up was death event. Survival of the whole group and the two subgroups was analyzed statistically by Kaplan-Meier method. Results All RFA procedures was given under intravenous anesthesia and local anesthesia, no severe complication was noted. Lesions in 16 patients were completely ablated after single or multiple sections of RFA+TACE. Twenty patients were in the partially ablated group. Follow up time was 25±10 (10-40) months. Twenty-three patients died and 13 kept alive during the follow up time. The estimated median survival time was 27 month (95%CI: 24-32 months). Survival ration at 1, 2, 3 years for the whole group was 91.7%(33/36),55.5%(20/36),36.1%(13/36) for the whole group. The 3 years survival for complete and partial ablation group was 75.0%(12/16),5.0%(1/20),there was a significant difference between the two groups(P<0.01). Conclusion For patients with hepatic metastasis, RFA+TACE can effectively control the local lesion. Complete ablation is the key point for a better survival.