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Famitinib is a tyrosine kinase inhibitor under clinical investigation for the treatment of solid tumors. Here, a 3‐period crossover trial investigated the effect of high‐fat or low‐fat food intake on the single‐dose pharmacokinetic properties of oral famitinib. Twenty‐four healthy Chinese participants were enrolled and received a single 25‐mg dose of famitinib malate capsule following a high‐fat or low‐fat breakfast before dosing. Blood samples were collected before dosing (0 hour) to 192 hours after dosing, and famitinib concentrations in plasma were determined with validated liquid chromatography–tandem mass spectrometry. Compared with the fasting condition, the geometric mean ratios for low‐fat/fasting were 98.6%, 107.7%, and 107.5% for maximum plasma concentration, area under the plasma concentration–time curve (AUC) over the dosing interval, and AUC from time 0 to infinity, respectively. Those for high‐fat/fasting were 84.4%, 105.0%, and 105.1% for maximum plasma concentration, AUC over the dosing interval, and AUC from time 0 to infinity, respectively. There was no significant difference in adverse events between fasting and fed conditions, and no serious adverse events occurred during the trial. In conclusion, oral famitinib bioavailability is not affected by food intake, implying that patients with cancer do not need to consider dietary status when using famitinib. This is considered important for convenience and treatment compliance. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the pharmacokinetic characteristics and safety of dalpiciclib at 100‐, 125‐, and 150‐mg doses after process modification in healthy Chinese volunteers. This single‐center, randomized, open‐label, three‐dose, phase I clinical study was conducted in healthy Chinese adults. Thirty‐six volunteers were randomized to three groups, including groups administered 100, 125, and 150 mg of dalpiciclib, and each group contained an equal number of males and females. A single oral dose of dalpiciclib was administered to each group, and plasma concentrations were measured by a validated liquid chromatography‐tandem mass spectrometry method. The oral formulation of dalpiciclib was well absorbed, the plasma concentration reached the maximum concentration (Cmax) in 4–6 hours, and it was eliminated from plasma with a mean terminal half‐life of 42.9–45.5 hours after 100–150 mg was administered. Dalpiciclib exhibited safety and favorable pharmacokinetic profiles, supporting further investigations in phase II studies. The plasma exposure of dalpiciclib was dose‐dependent, with increasing doses in the range of 100–150 mg. [ABSTRACT FROM AUTHOR]

Aim: This trial (NCT04013048) investigated the metabolite profiles, mass balance and pharmacokinetics of fuzuloparib, a novel poly (ADP‐ribose) polymerase inhibitor, in subjects with advanced solid cancers. Methods: A single dose of 150 mg [14C]fuzuloparib was administered to five subjects with advanced solid cancers. Blood, urine and faecal samples were collected, analysed for radioactivity and unchanged fuzuloparib, and profiled for metabolites. The safety of the medicine was assessed during the study. Results: The maximum concentrations (Cmax) of the total radioactivity (TRA) and unchanged fuzuloparib in plasma were 5.39 μg eq./mL and 4.19 μg/mL, respectively, at approximately 4 hours post dose. The exposure (AUC0‐t) of fuzuloparib accounted for 70.7% of the TRA in plasma, and no single metabolite was observed accounting for more than 10% of the plasma TRA. The recovery of TRA in excreta was 103.3 ± 3.8% in 288 hours, including 59.1 ± 9.9% in urine and 44.2 ± 10.8% in faeces. Sixteen metabolites of fuzuloparib were identified, including mono‐oxidation (M1), hydrogenation (M2), di‐oxidation (M3), trioxidation (M4), glucuronidation (M5, M7, M8) and de‐ethylation (M6) products, and there was no specific binding between these metabolites and blood cells. Aliphatic hydroxylated fuzuloparib (M1‐1) was the primary metabolite in the excreta, accounting for more than 40% of the dose for subjects. There were no serious adverse events observed in the study. Conclusion: Fuzuloparib was widely metabolized and excreted completely through urine and faeces in subjects with advanced solid cancer. Unchanged fuzuloparib was indicated to be the primary drug‐related compound in circulation. [14C]fuzuloparib was well‐tolerated at the study dose. [ABSTRACT FROM AUTHOR]