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Objectives Due to its high morbidity, high mortality, and high disability, stroke has been the first cause of death and the major cause of adult disability in China. Natural borneol has been widely utilized in Traditional Chinese Medicine to promote drug absorption. Formononetin is a natural isoflavonoid with potent neuroprotective activity but poor brain delivery. Methods This study aimed to screen the optimum proportion that natural borneol promotes formononetin entry into the brain, evaluate the anti-cerebral ischaemia efficacy of formononetin/natural borneol combination in middle cerebral artery occlusion/reperfusion model rats, and clarify the possible mechanism for natural borneol's promoting formononetin delivery in the brain. Key findings Our studies exhibited that natural borneol remarkably promoted formononetin entry into the brain when combined with formononetin in a 1 : 1 molar ratio and notably improved neuro-behavioural scores and reduced the infarct of middle cerebral artery occlusion/reperfusion model rats. This study further discovered that the enhanced anti-cerebral ischaemia effect resulted from natural borneol increasing the permeability of the blood-brain barrier to elevate formononetin concentration in the brain rather than the pharmacodynamic synergy or addition between formononetin and natural borneol. Conclusions The study provides a good strategy to screen drug combinations for the treatment of brain disease by combining natural borneol with other drugs. [ABSTRACT FROM AUTHOR]

Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross, a traditional Chinese medicinal plant, is often used to treat various urologic disorders in China. P. capitata extracts (PCE) have been used in combination with levofloxacin (LVFX) to treat urinary tract infections (UTIs) for a long time. However, little is known about the absorption of LVFX and transporter expression in the intestine after combined treatment with PCE, restricting the development and utilization of PCE. In view of this, a UPLC-MS/MS method was established for the determination of LVFX in intestinal sac fluid samples and in situ intestinal circulation perfusate samples to explore the effect of PCE on the intestinal absorption characteristics of LVFX ex vivo and in vivo. To further evaluate the interaction between LVFX and PCE, western blotting, immunohistochemistry, and RT-qPCR were utilized to determine the expression levels of drug transporters (OATP1A2, P-gp, BCRP, and MRP2) involved in the intestinal absorption of LVFX after combined treatment with PCE. Using the everted intestinal sac model, the absorption rate constant (K a) and cumulative drug absorption (Q) of LVFX in each intestinal segment were significantly lower in groups treated with PCE than in the control group. K a at 2 h decreased most in the colon segment (from 0.088 to 0.016 µg/h·cm2), and Q at 2 h decreased most in the duodenum (from 213.29 to 33.92 µg). Using the intestinal circulation perfusion model, the K a value and percentage absorption rate (A) of LVFX in the small intestine decreased significantly when PCE and LVFX were used in combination. These results showed that PCE had a strong inhibitory effect on the absorption of LVFX in the rat small intestine (ex vivo and in vivo intestinal segments). In addition, PCE increased the protein and mRNA expression levels of efflux transporters (P-gp, BCRP, and MRP2) and decreased the expression of the uptake transporter OATP1A2 significantly. The effects increased as the PCE concentration increased. These findings indicated that PCE changed the absorption characteristics of levofloxacin, possibly by affecting the expression of transporters in the small intestine. In addition to revealing a herb–drug interaction (HDI) between PCE and LVFX, these results provide a basis for further studies of their clinical efficacy and mechanism of action. [Display omitted] • An UPLC-MS/MS method is established to clarify the HDIs between PCE and LVFX. • PCE can significantly decrease the absorption level of LVFX. • HDIs between PCE and LVFX are mediated by drug transporters. • It has laid the foundation for the development and utilization of PCE. [ABSTRACT FROM AUTHOR]

Background: This study was to observe the non-heme iron absorption and biological utilization from typical whole Chinese diets in young Chinese healthy urban men, and to observe if the iron absorption and utilization could be affected by the staple food patterns of Southern and Northern China. Materials and Methods: Twenty-two young urban men aged 18–24 years were recruited and randomly assigned to two groups in which the staple food was rice and steamed buns, respectively. Each subject received 3 meals containing approximately 3.25 mg stable 57FeSO4 (the ratio of 57Fe content in breakfast, lunch and dinner was 1:2:2) daily for 2 consecutive days. In addition, approximately 2.4 mg 58FeSO4 was administered intravenously to each subject at 30–60 min after dinner each day. Blood samples were collected from each subject to measure the enrichment of the 57Fe and 58Fe. Fourteen days after the experimental diet, non-heme iron absorption was assessed by measuring 57Fe incorporation into red blood cells, and absorbed iron utilization was determined according to the red blood cell incorporation of intravenously infused 58Fe SO4. Results: Non-heme iron intake values overall, and in the rice and steamed buns groups were 12.8 ±2.1, 11.3±1.3 and 14.3±1.5 mg, respectively; the mean 57Fe absorption rates were 11±7%, 13±7%, and 8±4%, respectively; and the mean infused 58Fe utilization rates were 85±8%, 84±6%, and 85±10%, respectively. There was no significantly difference in the iron intakes, and 57Fe absorption and infused 58Fe utilization rates between rice and steamed buns groups (all P>0.05). Conclusion: We present the non-heme iron absorption and utilization rates from typical whole Chinese diets among young Chinese healthy urban men, which was not affected by the representative staple food patterns of Southern and Northern China. This study will provide a basis for the setting of Chinese iron DRIs. [ABSTRACT FROM AUTHOR]

In Feb 2020, we developed a physiologically-based pharmacokinetic (PBPK) model of hydroxychloroquine (HCQ) and integrated in vitro anti-viral effect to support dosing design of HCQ in the treatment of COVID-19 patients in China. This, along with emerging research and clinical findings, supported broader uptake of HCQ as a potential treatment for COVID-19 globally at the beginning of the pandemics. Therefore, many COVID-19 patients have been or will be exposed to HCQ, including specific populations with underlying intrinsic and/or extrinsic characteristics that may affect the disposition and drug actions of HCQ. It is critical to update our PBPK model of HCQ with adequate drug absorption and disposition mechanisms to support optimal dosing of HCQ in these specific populations. We conducted relevant in vitro and in vivo experiments to support HCQ PBPK model update. Different aspects of this model are validated using PK study from 11 published references. With parameterization informed by results from monkeys, a permeability-limited lung model is employed to describe HCQ distribution in the lung tissues. The updated model is applied to optimize HCQ dosing regimens for specific populations, including those taking concomitant medications. In order to meet predefined HCQ exposure target, HCQ dose may need to be reduced in young children, elderly subjects with organ impairment and/or coadministration with a strong CYP2C8/CYP2D6/CYP3A4 inhibitor, and be increased in pregnant women. The updated HCQ PBPK model informed by new metabolism and distribution data can be used to effectively support dosing recommendations for clinical trials in specific COVID-19 patients and treatment of patients with malaria or autoimmune diseases. [ABSTRACT FROM AUTHOR]