ABSTRACT
Abstract@#By reviewing the advocacy framework and implementation path of global adolescent health promotion, summarizing the main health problems of adolescents worldwide and current status of adolescent health care services in China, an ecological model of adolescent health care was concluded according to the demands of adolescents towards health care services. A comprehensive intervention strategy, ie. multi sector cooperation, community participation and integration of hospital, school, community and family, etc, has been put forward to promote the health and sustainable development of adolescents.
ABSTRACT
Podophyllotoxin (PPT) and its derivatives exert significant anti-cancer activities, and one derivative etoposide is often utilized to treat various cancers in the clinic. The aim of the present study is to investigate the inhibitory effects of PPT on major cytochrome P450 (CYP) isoforms in human livers. Inhibition of CYP3A4, CYP2C9, CYP2C8, CYP2D6, CYP2E1 and CYP2A6 by PPT was investigated in the human liver microsomal system. Time-dependent inhibition of CYP3A4 by PPT was also evaluated. The results showed that PPT strongly exhibited inhibitory effects on CYP3A4 and CYP2C9 in a concentration-dependent manner. Half inhibition concentration (IC50) was 1.1±0.3 and 4.6±0.3 μM for CYP3A4 and CYP2C9, respectively. Inhibition kinetic analysis showed that PPT exhibited competitive inhibition towards CYP3A4 and CYP2C9 with Ki of 1.6 and 2.0 μM, respectively. Additionally, PPT exerted time-dependent inhibition towards CYP3A4 and the kinetic parameters were 4.4±2.1 μM and 0.06±0.01 min–1 for KI and kinact, respectively. Our experimental data indicate that potential drug–drug interaction (DDI) might exist when PPT is co-administered with the substrates which mainly undergo CYP3A4- or CYP2C9-mediated metabolism.