RESUMEN
Delicaflavone (DF), a natural active ingredient from Selaginella doederleinii Hieron, has been reported to have favorable anticancer effects and is thus considered a potential anticancer agent. However, its pharmacokinetics and plasma protein binding properties remain unknown. Here, we investigated the pharmacokinetic profile of DF in rats using a validated HPLC-MS/MS methods, as well as its human serum albumin (HSA) binding properties through multi-spectroscopic and in silico methods. The results showed that DF was rapidly eliminated and had a widespread tissue distribution after intravenous administration. DF showed linear dynamics in the dose range of 30-60 mg/kg and poor oral bioavailability. The major distribution tissues of DF were the liver, lungs, and kidneys. Ultraviolet and fluorescence spectroscopy and molecular docking demonstrated that DF had a static quenching effect on HSA, with one binding site, and relatively strong binding constants. Thermodynamic analysis of the binding data revealed that hydrogen bonding and van der Waals interactions played major roles in binding. The results of this study further our understanding of the pharmacokinetic and plasma protein binding properties of the potential anticancer agent DF and shed light on pharmacological strategies that may be useful for the development of novel cancer therapeutics.
RESUMEN
BACKGROUND: This study aimed to analyze the cost-effectiveness of crizotinib versus ceritinib or alectinib as first-line-targeted drug therapy for anaplastic lymphoma kinase-positive advanced non-small cell lung cancer in China. METHODS: The Markov model was used to simulate the medical cost and quality-adjusted life years (QALYs) of patients using crizotinib, ceritinib, or alectinib over a 10-year period by establishing three health states: progression-free, post-progression, and death. Randomized controlled clinical data were collected from the open-label, randomized phase 3 trials ALEX and ASCEND-4. Cost and utility values were derived from local charges and literature. Sensitivity analyses included one-way and probabilistic sensitivity analyses. RESULTS: Compared with patients who used crizotinib as first-line treatment, patients in the ceritinib and alectinib groups yielded an additional 1.32 and 3.30 QALYs with an incremental cost of $84,728.20 and $339,114.36, respectively. Thus, the incremental cost-effectiveness ratio (ICER) was $64,398.83 and $102,675.74 per QALY in the ceritinib and alectinib groups, respectively. Alectinib was estimated to be more effective (4.68 QALY) and more costly ($432,063.06) with an ICER of $128,019.42 per QALY compared with ceritinib (2.69 QALY and $177,676.90). Results were robust to deterministic and probabilistic sensitivity analyses. CONCLUSION: As a first-line treatment regimen, ceritinib and alectinib can extend the survival time of patients compared with crizotinib, but the medical cost also increases accordingly. According to the World Health Organization's three-percent GDP measurement, first-line treatment with Crizotinib is the most cost-effective.