ABSTRACT
OBJECTIVE: To study the pharmacokinetics of pirfenidone in Chinese healthy volunteer after a single dose and multiple-dose administration. METHODS: Twelve Chinese healthy volunteers were randomly divided into low, medium and high dose groups(200, 400, 600 mg). The multiple-dose group was administrated with pirfenidione 400 mg three times daily for 5 d. Intensive blood sampling was performed from 12 volunteers within 12 h after the single dosing and the last dose of the multiple dosing. HPLC-MS/MS was used to determine the plasma concentrations of pirfenidone. The pharmacokinetic parameters were calculated by DAS software. RESULTS: The main pharmacokinetic parameters of pirfenidone after single-dose administration of 200, 400, 600 mg qd as follows: ρmax were(5.00 ± 1.42), (9.43 ± 2.74) and(14.14 ±3.36)mg · L-1; tmax were(0.57 ±0.33), (0.60 ± 0.30) and(0.60 ± 0.38) h; t½ were(2.16 ±0.77), (2.15 ±0.75) and (2.01 ±0.76)h; AUC0-∞ were(13.87 ±7.79), (29.26 ± 12.02) and (45.85 ± 20.25)mg · h · L-1; AUC0-12 were (13.27 ±7.08), (27.92 ± 10.56) and(43.98 ± 18.14) mg · h · L-1, respectively. The main pharmacokinetic parameters after 400 mg tid for 5 d were as follows: ρmax was(9.46 ±2.77) mg · L-1, ρmin was(1.14 ± 1.11) mg · L-1, tmax was(0.52 ± 0.34) h, t½ was (1.93 ± 0.63) h, AUC0-∞ was (26.74 ± 13.49) mg · h · L-1, AUC0-12 was (25.79 ± 12.34)mg · h · L-1, AUCss was(23.53 ± 10.59)mg · h · L-1. CONCLUSION: The pharmacokinetic parameters of pirfenidone show that ρmax and AUC were linear in the dose range from 200 - 600 mg and the pharmacokinetic parameters were similar as reference.
ABSTRACT
Objective To analyse the causes of perinatal death and explore the preventive measures to reduce the perinatal mortality.Methods The cases with perinatal death in this hospital from January 2005 to December 2006 were reviewed to analyse the causes of death by categorization and sum-up.Results There were 166 cases with perinatal death and the mortality rate was 27.08‰,including 126 cases with fatal death,which accounted for 75.90%.In the analysis of dead causes,the first one was birth defects,which suffered 69 cases,41.57% of all,and mostly were with fetus edema syndrome.The cord factors had been elevated to the second cause,which suffered 51 cases,30.72% of all.Conclusion Improving the consciousness of gestational monitoring and self-care,strengthening the prenatal diagnosis and genetic counseling,controlling the perinatal birth defects,monitoring mother and fetus by poly-parameter and stopping the pregnancy in time can reduce perinatal death effectively.