The metabolism of the pyrethroids deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes.
DLM, CPM and TPM were metabolised by human CYP2B6 and CYP2C19, with the highest apparent intrinsic clearance (CLint) values for pyrethroid metabolism being observed with CYP2C19. Other CYP enzymes contributing to the metabolism of one or more of the three pyrethroids were CYP1A2, CYP2C8, CYP2C9*1, CYP2D6*1, CYP3A4 and CYP3A5. None of the pyrethroids were metabolised by CYP2A6, CYP2E1, CYP3A7 or CYP4A11.
DLM, CPM and TPM were metabolised by both human CES1 and CES2 enzymes.
Apparent CLint values for pyrethroid metabolism by CYP and CES enzymes were scaled to per gram of adult human liver using abundance values for microsomal CYP enzymes and for CES enzymes in liver microsomes and cytosol. TPM had the highest and CPM the lowest apparent CLint values for total metabolism (CYP and CES enzymes) per gram of adult human liver.
Due to their higher abundance, all three pyrethroids were extensively metabolised by CES enzymes in adult human liver, with CYP enzymes only accounting for 2%, 10% and 1% of total metabolism for DLM, CPM and TPM, respectively.
The objective of the study was to define factors associated with adolescent and young adult (AYA) experiences with private time and having discussed confidentiality and the impact of these experiences on improving delivery of clinical preventive services.
Methods
In 2016, a nationally representative sample of 1,918 US AYAs (13- to 26-year-olds) was surveyed. Survey questionnaire domains were based on prior research and Fishers' information-motivation-behavior skills conceptual model. Data were weighted to represent US households with AYA and analyzed to identify factors independently associated with ever experiencing private time and discussions of confidentiality with a regular health-care provider (HCP). We examined the association of these experiences on AYA attitudes about health care.
Results
Fifty-five percent of female and 49% of male AYA reported ever having had private time with an HCP and 55% of female and 44% of male AYA had spoken to an HCP about confidentiality. Independent predictors of having experienced private time and confidentiality included older age, race, higher household income, gender of the provider, amount of years with the provider, and involvement in risk behaviors. AYA who had experienced private time and confidentiality discussions had more positive attitudes about their providers, were more willing and comfortable discussing sensitive topics, and thought that these discussions should happen at younger ages.
Conclusions
Although confidentiality and private time are important to AYA, many are not experiencing these components of care. Providing private time and discussions of confidentiality can improve the delivery of health care for young people by enhancing positive youth attitudes about preventive care. 相似文献
The objective of this study was to investigate the absorption behavior of chikusetsusaponin IVa (CHS‐IVa) in the rat intestine using single‐pass intestinal perfusion (SPIP) and to classify CHS‐IVa into the biopharmaceutics classification system (BCS). The equilibrium solubility of CHS‐IVa was determined by the shaker method. The absorption mechanism of CHS‐IVa in the intestine was studied by comparing the Peff of different concentrations of CHS‐IVa. The intestinal site dependence of CHS‐IVa absorption was studied by comparing the Peff of the same concentration of CHS‐IVa in different intestinal segments. The relationship between CHS‐IVa and intestinal efflux protein was studied by perfusion with an efflux protein inhibitor. The permeability of CHS‐IVa was investigated by comparing the Peff of CHS‐IVa and the reported value. The solubility of CHS‐IVa over the pH range 1.0–7.5 was 14.4 ± 0.29 to 16.9 ± 0.34 mg/ml. The Peff of CHS‐IVa in the duodenum was 1.76 × 10?3 to 2.00 × 10?3 cm/min. The Peff of CHS‐IVa in the jejunum was 1.26 × 10?3 to 1.39 × 10?3 cm/min. The Peff of CHS‐IVa in the ileum was 1.25 × 10?3 to 1.31 × 10?3 cm/min. The Peff of CHS‐IVa in the colon was 1.02 × 10?3 to 1.08 × 10?3 cm/min. There was no statistical difference of the Peff in the four segments at different CHS‐IVa concentrations. The Peff of CHS‐IVa (0.07, 0.7 and 7.0 mg/ml) were all notably smaller than the reported Peff (3.00 × 10?3 cm/min) in the jejunum. The Peff of CHS‐IVa was not influenced by verapamil (P‐gp inhibitor), indomethacin (MRP inhibitor) and pantoprazole (BCRP inhibitor). CHS‐IVa was classified as high solubility, low permeability and BCS III. The main absorptive tracts were the upper intestinal tracts and the rank order of intestinal permeability was duodenum > jejunum ≈ ileum > colon. The transport mechanism of CHS‐IVa in all intestinal segments might be primarily passive transport. CHS‐IVa was not a substrate of P‐gp, MRP and BCRP. 相似文献