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Objective: To compare the pharmacokinetics and bioavailability of pirfenidone in the fasted and fed states in healthy volunteers. Methods: An open-label, randomized crossover study was conducted in 12 healthy subjects. Food effects were examined by comparing pharmacokinetic data of pirfenidone after administration of a single oral 400 mg dose under fasted or fed conditions. Plas-ma pirfenidone concentration was determined by an HPLC method and its pharmacokinetic parameters were calculated with DAS v2. 0 software. Results: Under fasted and fed conditions, the concentration-time profiles of pirfenidone were fitted a one-compartment model and the pharmacokinetic parameters were as follows: t1/2were (2. 16 ± 0. 47) and (2. 05 ± 0. 42) h;tmaxwere(0. 69 ± 0. 16)and (1. 46 ± 0. 40)h;Cmaxwere (12. 95 ± 1. 79) and (9. 16 ± 2. 87) mg·L-1;AUC0-12were (44. 97 ± 15. 06) and (36. 19 ± 14. 44) mg·h·L-1;AUC0-∞were (46. 55 ± 16. 79) and (37. 41 ± 15. 43) mg·h·L-1, respectively. When compared with that of the fasted group, tmaxwas significantly increased (P<0. 001) while Cmaxand AUC were remarkedly decreased in the fed group (P<0. 001 and P<0. 01, respectively). Conclusion: Concomitant food intake significantly influences the pharmacokinetics and bioavail-ability of pirfenidone as indicated by reducing its extent and rate of absorption, which is associated with better tolerability.
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To determine the pharmacokinetics and bioequivalence of epinastine (EPN) hydrochloride, a promising histamine H1 receptor antagonist, in healthy Chinese volunteers under fasting conditions. METHODS: EPN hydrochloride test and reference tablets were administered as a single dose on two treatment days separated by a 1-week washout period. After dosing, serial blood samples were collected for a period of 36 h, and plasma EPN hydrochloride concentrations were determined by a validated reversed-phase HPLC method and pharmacokinetic parameters were calculated with DAS software. RESULTS: Plasma concentration-time profiles were adequately described by a two-compartment open model. The compound was rapidly absorbed and cleared slowly from plasma with a half-life of approximately 10 h. The main pharmacokinetic parameters of EPN hydrochloride test and reference tablets were as follow: tmax were (2.2±0.5) and (2.0±0.4)h, Cmax were (66±16)and (68±13)μg/L, t1/2 were(10.1±1.3) and (10.4±2.4)h, AUC0-36 were (592±88) and (601±94)μg·h·L-1, respectively. The relative bioavailability of test tablets was (99±13)%. CONCLUSION: The results indicate that the two formulations of EPN hydrochloride tablets are bioequivalent in the rate and extent of absorption.
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AIM: To compare the bioavailability of the test and reference formulation of secnidazole (2 g) tablets under fasting conditions. METHODS: This bioequivalence study was carried out in 20 healthy male Chinese volunteers according to a single dose, two-sequence, crossover randomized design. Fifteen blood samples per period were collected over 96 h, and plasma secnidazole concentrations were determined by locally validated high performance liquid chromatography (HPLC) assay and pharmacokinetic parameters were analyzed by the non-compartmental and compartmental methods. RESULTS: Plasma concentration-time profiles were adequately described by a one-compartment open model with first-order absorption. The main pharmacokinetic parameters of secnidazole test and reference tablets were as follows: tmax were (2.30±1.06) and (2.28±1.10) h, Cmax were (49.63±6.35) and (46.17±4.24) mg/L, t1/2 were (28.84±3.41) and (29.05±4.01) h, AUC0-96 were (1832.06±180.15) and (1847.14±204.14) mg·h-1·L-1, respectively. The relative bioavailability of test tablets was (99.99±11.92)%. CONCLUSION: The results indicate that the two formulations of secnidazole tablets are bioequivalent in the rate and extent of absorption.
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OBJECTIVE:To establish a HPLC method for the determination of mycophenolic acid (MPA) in human plasma and to study its pharmacokinetics in human body.METHODS:After sedimentation by methanol,plasma sample of MPA was determined directly on Symmetry Shield C18 column with column temperature at 30℃,detective wavelength at 218mn and sample size at 20?L.The mobile phase consisted of acetonitrile-water-triethylamine(40∶60∶0.3) with a flow rate of 1.0mL?min-1.RESULTS:The calibration curve was linear over the range of 0.2～50mg?L-1(r=0.999 6)and the limit of quantitation was 0.2mg?L-1.The mean methodological recovery was 101.94% and the mean extraction recovery was 87.06%.The RSD of both the intra-day and the inter-day were less than 6%.The pharmacokinetic study showed that MPA had enterohepatic circulation in human body,which resulted in the occurrence of double peaks,and the concentration-time curves of MPA were fitted to one-compartment open model.CONCLUSION:This method is sensitive,rapid,specific,accurate and precise,and can be used for the study of pharmacokinetics of MPA.
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AIM: To study pharmacokinetics and relative bioavailability of pantoprazole sodium enteric-coated test and reference tablets in healthy volunteers. METHODS: A single oral dose of 40 mg pantoprazole sodium enteric-coated test and reference tablets were given to 20 male healthy volunteers in a randomized two-way crossover design. Plasma concentrations of pantoprazole were determined by HPLC method. Pharmacokinetic parameters and relative bioavailability were calculated with DAS program to evaluate the bioequivalence of the two preparations. RESULTS: Plasma concentration-time profiles were adequately described by a two-compartment open model. The main pharmacokinetic parameters of pantoprazole sodium test and reference tablets were as follow: The values of Tmax were (3.18±0.54) and (3.30±0.47) h, Cmax were (2.98±0.83) and (2.91±0.87) mg·L-1, T1/2β were (1.86±0.41) and (1.72±0.48) h, AUC0-t were (9.51±3.71) and (9.77±4.55) mg·h·L-1, respectively. The relative bioavailability of test tablets was (102.3±19.6)%. CONCLUSION: The two preparations of pantoprazole sodium are bioequivalent.
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OBJECTIVE: To establish a RP-HPLC method for the determination of 5-fluorouracil(5-Fu)in magnetic micropheres (MMS), and to evaluate the target ability of 5-Fu magnetic microspheres in mice. METHODS: 5-Fu-MMS was digested with 0.5% pepsin, and then free 5-Fu was extracted from tissue with ethyl acetate, and detected by a validated RP-HPLC method. RESULTS: The calibration curve was linear over the range of 0.1～25mg?L-1 and the limit of quantization was 0.1mg?L-1. The tissue distribution of 5-Fu-MMS in the liver was significantly increased as compared to control(P