RESUMEN
@#To conduct the characterization of its pharmacokinetics in rats of nifedipine sustained-release pellets and to study the relationship between the pellets and CYP3A4 activity. A gradient HPLC method was developed to simultaneously determine 6β-hydroxycortisol and hydrocortisone. CYP3A4 activity of rats was quantified by urinary ratio of 6β-hydroxycortisol/hydrocortisone after intravenous injection of hydrocortisone as a biomarker. HPLC method was also developed to quantify the drug concentration in plasma of rats, and the studies of pharmacokinetics were performed after oral administration of single dose of two formulations: Nifedipine matrix sustained-release pellets and nifedipine tablet(using as control). The results showed that the ratio of ten rats was 0. 271±0. 129. cmax of nifedipine sustained-release pellets decreases by nearly 70%, tmax significantly increased by 400% and t1/2 and MRT significantly increased by 230% compared to control. Nifedipine sustained-release pellets had a significant sustained-release property compared to the control and CYP3A4 activity affected its pharmacokinetics behavior.
RESUMEN
Human cytochrome P450 (CYP) 3A ,which is widely involved in the various drug metabolism ,is most abun-dant in liver and intestine .The activity of CYP3A enzyme may be induced or inhibited in the process of drug metabolisms ,and affect the metabolism of other CYP3A substrates and modulators vice versa .At present ,in vitro probe drugs and in vivo bio-markers are both available to evaluate the activity of CYP 3A enzyme .The former requires oral probe drugs ,the latter does not need for those drugs and just allows laboratory technicians to detect endogenous substrates ,such as 4β-hydroxycholesterol and 6β-hydroxycortisol .As reported ,studies on CYP3A help to explain the inter-individually variability in drug metabolism ,to in-dicate dose adjustments in combination regimens when drug interactions exist ,to predict drug efficacy and toxicity reaction for providing theoretical guidance for individualized medication ,and to reduce market risk of new drugs for the potential drug inter-actions .We summarized these two kinds of endogenous biomarkers and their clinical application in this review .
RESUMEN
OBJECTIVE: To investigate the CYP3A activity and its characteristics of distribution in the pre-school children in Xiamen. METHODS: Using hydrocortisone as a noninvasive probe, urine concentrations of hydrocoritisone ydrocortisone and 6β-hydroxycortisol were determined by HPLC method. The urinary ratio of 6β-hydroxycortisol/hydrocortisone was used to quantify CYP3A activity. RESULTS: The CYP3A activity in the 287 healty children showed a skewed to the left distribution. The median value was 2.61 and the value of quartile range was 3.97. CONCLUSION: There is no significant difference in CYP3A activity in gender. With increasing of ages, the CYP3A activity shows the decreasing tendency. The results show a statistic correlation between the ages and CYP3A activity. The value of CYP3A activity in age 3 group is higher than age 4 group.