Quantitative approach for calculation of pharmacodynamic interactions and simulation of combined response / 中国中药杂志

<p><b>OBJECTIVE</b>An approach is set up to calculate pharmacodynamic interaction and simulate the combined response.</p><p><b>METHOD</b>An orthogonal design with 1-level = high dose and 2-level = low dose was adopted. An example of the compound with four components was applied to evaluate this quantitative approach. The bias was evaluated by the both scatter plots.</p><p><b>RESULT</b>This approach can calculate the value of each component with different dose by its contribution to combined response, and the value is related to the importance of a compound. Drug interactions were evaluated among the combinations in each group. The prediction model performed well and simulated the combined response in the different of components in combination.</p><p><b>CONCLUSION</b>The approach can be used in the similar research, and it also provides predictions of component combinations from the other studies by simulation.</p>

XS0601 reduces the incidence of restenosis: a prospective study of 335 patients undergoing percutaneous coronary intervention in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>XS0601, consisting of active ingredients (Chuangxiongol and paeoniflorin), has been shown to inhibit arterial neointimal hyperplasia in animal models and in preliminary human studies. The objective of this study was to evaluate the safety and efficacy of XS0601 in preventing restenosis following percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>A multi-center, randomized, double-blind, placebo-controlled trial was conducted. A total of 335 patients were randomized into treatment with the oral administration of XS0601, or a placebo for 6 months after successful PCI. Angiographic follow-up was scheduled at 6 months, and clinical follow-ups performed at 1, 3 and 6 months after PCI. The primary end point was angiographic restenosis. The secondary end points were the combined incidence of death, target lesion nonfatal myocardial infarction, repeat angioplasty, and coronary artery bypass graft surgery.</p><p><b>RESULTS</b>A total of 308 patients (91.9%) completed the study and 145 cases (47.1%) received angiographic follow-up. The restenosis rates were significantly reduced in the XS0601 group as compared with the placebo group (26.0% vs. 47.2%, P < 0.05), and the minimum lumen diameter (MLD) was greater [(2.08 +/- 0.89) mm for XS0601 vs. (1.73 +/- 0.94) mm for placebo, P < 0.05]. XS0601 also significantly reduced the combined incidence of major adverse cardiac event (10.4% in the XS0601 group vs. 22.7% in the placebo group, P < 0.05). The incidence of recurrent angina at 3 and 6 months after PCI was also significantly reduced in XS0601 group (7.1% and 11.0%) as compared with those in placebo group (19.5% and 42.9%) (P < 0.05). No significant side effects occurred within the 6-month follow-up period in the XS0601 group.</p><p><b>CONCLUSION</b>Administration of XS0601 for 6 months is demonstrated to be safe and effective in reducing restenosis in post-PCI patients.</p>

A nomogram for prediction of absorption rate coefficient / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Previous studies have suggested that nomogram can simplize complicated calculations of several variables. A simple nomogram was constructed to estimate absorption rate coefficient (k(a)) by using the peak time (tpeak) and the elimination rate coefficient (k(e)) of drugs administered orally.</p><p><b>METHODS</b>The nomogram was based on the plasma concentration-time (C-T) curve equation and the function relation between t(peak), k(a) and k(e). A mathematical analysis was presented for the construction of single chart nomogram. To check the degree of accuracy of the developed nomogram, we used it to analyze retrospective profiles of 46 drugs and compared the ka values obtained graphically and those calculated by numerically solving the descriptive equation. In addition, we measured the carbocisteine concentration of 18 healthy volunteers by HPLC with fluorescence detection. To analyze performance error, the measured carbocisteine concentrations were compared with predicted concentrations by the ka obtained from the nomograms along with the other pharmacokinetic parameters.</p><p><b>RESULTS</b>The estimated of k(a) values from nomograms were in very close proximity with the numerical values. The performance error was as follows: median performance error (MDPE) and median absolute performance error (MDAPE) were 1.32% and 18.15%, respectively.</p><p><b>CONCLUSIONS</b>The developed nomogram is accurate and reliable. The size of performance error meets the demand of clinical pharmacokinetics. Therefore, the nomograms can offer another convenient and easy method for rational individualized dosage regimens.</p>