ABSTRACT
Quercetin could affect both the in vivo and in vitro transport of a variety of commonly used drugs by modulating the uptake transporter organic anion transporter polypeptides (OATPs), organic anion transporters (OATs), efflux transporter P-glycoprotein (P-gp), multidrug resistance-related protein (MRP) and breast cancer resistance protein (BCRP), respectively. Quercetin can regulate various drug transporters, thereby affecting other drugs in vivo process.
ABSTRACT
OBJECTIVE: To investigate the effect of high-fat and high-calorie diets on pharmacokinetics of cefuroxime axetil in healthy Chinese subjects. METHODS: A randomized, open-label, single dose and two-way crossover clinical study was conducted. Twelve healthy subjects were randomly divided into two groups, each of which includes six males, then they were given 250 mg of cefuroxime axetil respectively before and after meal. Blood samples were collected at different time points before and after drug administration. The concentration of cefuroxime in plasma was determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated by DAS3.2.8 and were analyzed by DAS3.2.8 and SPSS19.0. RESULTS: The main pharmacokinetic parameters of fasting and postprandial were as follows: AUC0-t was (11 402.8±3 556.7) and (18 565.7±2 917.9) ng·h·mL-1, AUC0-∞ was (11 492.5±3 581.8) and (18 754.7±2 885.6) ng·h·mL-1, ρmax was (3 406.7±1 188.9) and (5 439.2±1 118.2) ng·mL-1, tmax was (2.01±0.64) and (2.08±0.79) h, t1/2 was (1.66±0.38) and (1.60±0.60) h, respectively. The main pharmacokinetic parameters between fasting and high-fat meal groups were analyzed by SPSS19.0 software. There was significant difference in AUC0-t, AUC0-∞ and ρmax(P0.05). The ρmax and AUC were increased by 59.7% and 63.2% respectively, tmax is almost unchanged. The equivalence analysis was performed with DAS.3.2.8 software, the 90% confidence intervals for the ratios of AUC0-t, AUC0-∞ and ρmax for the postprandial/fasting were 137.6%-217.5%, 138.4%-217.3%, 135.4%-207.6%, respectively. None of them fall within the acceptable interval of 80%-125%. CONCLUSION: High-fat and high-calorie diets can significantly improve the extent of absorption of cefuroxime axetil in vivo, but does not affect the absorption rate of cefuroxime axetil.