Résumé
OBJECTIVE To evaluate the efficacy, safety and cost-effectiveness of generic drugs and original drugs of voriconazole. METHODS The information of patients who used voriconazole generic drugs selected in National Centralized Drug Procurement (generic drug group) or non-selected original drugs (original drug group) in the treatment of fungal infection was collected from the our hospital. The propensity score matching was carried out to eliminate bias. The comprehensive efficacy was evaluated according to clinical efficacy, image findings and microbiological test, and stratified analysis of different populations was conducted based on fungal species, underlying diseases, etc., the efficacy of different stratifications was evaluated. Evaluation of safety was performed by using the incidence of adverse reactions. The total cost, defined daily doses (DDDs) and defined daily dose cost (DDDc) were used to evaluate the cost-effectiveness. RESULTS A total of 436 patients were included, and there were 190 patients in each group after matching. In terms of efficacy, the effective rates of voriconazole generic drugs and original drugs were 62.63% and 59.47% (P=0.528); in terms of safety, the incidence of adverse reactions caused by generic drugs and original drugs of voriconazole was 13.68% and 7.89%, respectively(P=0.069). In terms of cost-effectiveness, the average total cost of generic drugs was 4 636.26 yuan, and that of original drugs was 8 613.20 yuan (P<0.001). After the implementation of National Centralized Drug Procurement, replacement rate of generic drugs increased to 87.30%, and DDDc decreased by 59.08%. CONCLUSIONS The efficacy and safety of voriconazole generic drugs are similar to those of original drugs in the treatment of fungal infection, and it is more cost-effective in terms of treatment cost.
Résumé
<p><b>OBJECTIVE</b>To synthesize novel cyanopyrrolidine-bearing compounds as dipeptidyl peptidase 4 (DPP4) inhibitors and characterize their biological activities in vitro.</p><p><b>METHODS</b>Eleven analogues of carbonitrilpyrrolidine were designed and synthesized by substitution reaction of (S)-2-(2-cyanopyrrolidin-1-yl)acetyl bromide with substituted phenyl piperazine pyridazinones.</p><p><b>RESULTS</b>The structures of the compounds were characterized by (1)H-NMR and MS spectra. Biological evaluation indicated that most of the compounds exhibited moderate inhibitory activities against DPP4.</p><p><b>CONCLUSION</b>The preliminary bioassay indicates that all the synthesized compounds have moderate DPP-4 inhibition activity, especially the compounds 1j and 1k with inhibition rates reaching 26.14% and 34.15% at the concentration of 1×10(5) nmol/L, respectively.</p>