Effects of Rifampicin On Pyrotinib Maleate Pharmacokinetics In Healthy Subjects

Purpose: Pyrotinib (PTN) is primarily metabolized by cytochrome P450 (CYP)3A4 isozyme. Rifampicin (RIF) is a strong CYP3A4 inducer. Thus, the effect of oral RIF on PTN pharmacokinetics (PK) was evaluated to provide dose recommendation when co-administered.Method: This phase I, open-label study investigated the effects of steady-state RIF administration on single-dose PK of PTN, in 18 healthy participants who received PTN 400 mg single doses on days 1 and 13, and were administrated with RIF 600 mg qd on days 6-16. Each dose for RIF was administrated on an empty stomach, PTN were administrated orally in the morning 30 min after the start of the standard meal. Serial PK samples for PTN were collected on day 1 and day 13. Plasma PTN PK parameters were determined with non-compartmental analysis. Geometric least-squares mean ratios (GMRs) and 90% confidence intervals (CIs) were generated by the mixed-effected model for within-subject treatment comparisons. Safety assessments were performed throughout the study.Results: Eighteen subjects were enrolled and 15 completed the study. RIF significantly reduced PTN exposure: GMRs (90 % CI) for PTN + RIF versus PTN alone were 0.04 (0.034,0.049), 0.04 (0.037,0.054), and 0.11 (0.09,0.124) for area under the curve from time zero to time of last quantifiable concentration (AUC0-t), area under the curve from time zero to infinity (AUC0-∞ ), and maximum observed plasma concentration(Cmax), respectively. PTN alone and co-administered with RIF was well tolerated.Conclusion: Concurrent administration of PTN and RIF was associated with significantly decreased systemic exposure to PTN. The findings suggest that concomitant strong CYP3A4 inducers should be avoided during PTN treatment. Concurrent administration of PTN and RIF was well tolerated.

A Comparison of the Nutrient Content of Standard and Vegetarian Childcare Lunches

Objectives As consumer interest in plant-based eating has increased, requests for meatless childcare meals have become increasingly common. Although vegetarian meals can be nutrient dense, without proper planning, nutrient inadequacies may occur. The objective of this study was to compare the nutrient content of standard childcare lunches with that of vegetarian alternative lunches. Methods Data was obtained from childcare centers participating in the Child and Adult Care Food Program and regularly providing a vegetarian meal alternative in addition to their standard meal. Centers that agreed to participate received unscheduled calls in which they were asked to provide menu and food preparation details for both the standard meal and for the vegetarian option served at lunch. Student's t-tests (P ≤ .05) were used to detect differences in nutrient content. Nutrient values (95% CI) for each set of meals were then compared to reference values representing one-third the Dietary Reference Intake for 3-year-olds. Results Seven childcare centers provided detailed information for a total of 27 meals. Vegetarian meal substitutions included, beans, vegetarian meat patties, tofu, and sunflower seed butter. However, the most common substitution was cheese which was used to fulfill all or part of the meat/meat-alternative requirement in 70.4% of the meals (n = 19). Mean values for energy, protein, fiber, vitamin A, vitamin D, iron, total fat, saturated fat, iron, and vitamin B12 did not differ significantly between the two lunch options. The vegetarian lunches were higher in saturated fat (P = 0.04) and calcium (P < 0.001). Both lunch options met the reference value for vitamin A, vitamin D, vitamin B12, calcium, and protein. Iron content for both (95% CI: standard 1.61–2.17 mg; vegetarian 1.37–2.7 mg) was below the reference value of 2.31 mg. Conclusions Aside from the vegetarian lunches being higher in saturated fat, both meals provided comparable nutrient content. Both meal options could be improved upon by the inclusion of more iron-dense foods. The vegetarian meals could be improved upon with less cheese and more plant-based alternatives, such as such as lentils and beans which are good sources of protein but low in saturated fat. Funding Sources College of Health and Human Sciences and Dr. Carol Shanklin Graduate Research Enhancement Award, Kansas State University.

Effect of Gazpacho, Hummus and Ajoblanco on Satiety and Appetite in Adult Humans: A Randomised Crossover Study

Nowadays, overweight and obesity has reached an epidemic level around the world. With the aim to tackle them, an interesting strategy is the study of food and ingredients with satiety properties. In addition to reducing food and/or calorie intake, this type of foods must be included as part of a healthy diet. With regard to this, it is well known that the Mediterranean Diet (MD) is a feeding pattern that helps us to maintain good health, providing an adequate intake of micronutrients and active compounds. With this background, the main aim of this research was to identify MD foods with a high satiating potential capacity. For this purpose, three typical foods of the Mediterranean region, mainly based on vegetables, were selected: hummus, ajoblanco and gazpacho. As a control, white bread was used. Twenty-four human healthy volunteers consumed a standard breakfast followed by the different typical Mediterranean foods, and then the subjective sensation of hunger and satiety for each food was assessed by visual analogue scales (VAS) during 3 h. Subsequently, volunteers had ad libitum access to a standard meal. The results indicate that gazpacho showed the highest satiating scores, despite the fact that it was not the food that provided the highest protein or fibre amount. More studies of this type are needed to determine the proportion and/or combination of ingredients from these classical Mediterranean recipes that could enhance human satiety.

A Population Pharmacokinetic and Pharmacodynamic Model of CKD-519

CKD-519 is a selective and potent cholesteryl ester transfer protein (CETP) inhibitor that is being developed for dyslipidemia. Even though CKD-519 has shown potent CETP inhibition, the exposure of CKD-519 was highly varied, depending on food and dose. For highly variable exposure drugs, it is crucial to use modeling and simulation to plan proper dose selection. This study aimed to develop population pharmacokinetic (PK) and pharmacodynamics (PD) models of CKD-519 and to predict the proper dose of CKD-519 to achieve target levels for HDL-C and LDL-C using results from multiple dosing study of CKD-519 with a standard meal for two weeks in healthy subjects. The results showed that a 3-compartment with Erlang’s distribution, followed by the first-order absorption, adequately described CKD-519 PK, and the bioavailability, which decreased by dose and time was incorporated into the model (NONMEM version 7.3). After the PK model development, the CETP activity and cholesterol (HDL-C and LDL-C) levels were sequentially modeled using the turnover model, including the placebo effect. According to PK-PD simulation results, 200 to 400 mg of CKD-519 showing a 40% change in HDL-C and LDL-C from baselines was recommended for proof of concept studies in patients with dyslipidemia.

The Accuracy and Precision of the Continuously Stored Data from Flash Glucose Monitoring System in Type 2 Diabetes Patients during Standard Meal Tolerance Test

Background. The purpose of this study was to investigate the accuracy of the continuously stored data from the Abbott FreeStyle Libre flash glucose monitoring (FGM) system in Chinese diabetes patients during standard meal tests when glucose concentrations were rapidly changing. Subjects and Methods. Interstitial glucose levels were monitored for 14 days in 26 insulin-treated patients with type 2 diabetes using the FGM system. Standard meal tests were conducted to induce large glucose swings. Venous blood glucose (VBG) was tested at 0, 30, 60, and 120 min after standard meal tests in one middle day of the first and second weeks, respectively. The corresponding sensor glucose values were obtained from interpolating continuously stored data points. Assessment of accuracy was according to recent consensus recommendations with median absolute relative difference (MARD) and Clarke and Parkes error grid analysis (CEG and PEG). Results. Among 208 paired sensor-reference values, 100% were falling within zones A and B of the Clarke and Parkes error grid analysis. The overall MARD was 10.7% (SD, 7.8%). Weighted least squares regression analysis resulted in high agreement between the FGM sensor glucose and VBG readings. The overall MTT results showed that FGM was lower than actual VBG, with MAD of 22.1 mg/dL (1.2 mmol/L). At VBG rates of change of -1 to 0, 0 to 1, 1 to 2, and 2 to 3 mg/dl/min, MARD results were 11.4% (SD, 8.7%), 9.4% (SD, 6.5%), 9.9% (SD, 7.5%), and 9.5% (SD, 7.7%). At rapidly changing VBG concentrations (>3 mg/dl/min), MARD increased to 19.0%, which was significantly higher than slow changing BG groups. Conclusions. Continuously stored interstitial glucose measurements with the FGM system were found to be acceptable to evaluate VBG in terms of clinical decision during standard meal tests. The continuously stored data from the FGM system appeared to underestimate venous glucose and performed less well during rapid glucose changes.

The role of gastric emptying in β-carotene absorption during simulated in vitro digestion

IntroductionThe availability of β-carotene from provitamin A rich foods in order to improve the provision of vitamin A in humans through food-based approaches is an important factor in mitigating micronutrient deficiencies. However, the extent of intestinal absorption (and subsequent availability of carotenoids to target tissues) is dependent on meal preparation, components of the meal and other intrinsic factors during gastro-intestinal (GI) digestion. Gastric emptying (GE), dictated by the caloric value of a meal, has been suggested as a critical component in determining β-carotene absorption. Indeed, dietary intake of high energy meals may just unravel the underlying factors associated with low uptake of dietary carotenoids during digestion. While several studies have reported the uptake of β-carotene as an individual pure compound under different digestive conditions(1), very few studies have assessed the effects of dietary carotenoids embedded in an energy dense meal, as would normally be consumed, on GI transit time and subsequent nutrient release.Materials and MethodsIn this study, we investigated the role of meal composition, particularly its caloric value, in modulating gastric emptying and thus the absorption of β-carotene. A step-by-step in vitro semi-dynamic model that simulates adult gastric digestion(2) was used on a prepared standard meal whose caloric value was estimated based on the Atwater system as described elsewhere with the assumption that the caloric density of the meal will assume a linear GE rate of 2kcal/min.ResultsPreliminary results indicate that, short transit times of 40 minutes, mimicking early GE, have the highest concentration (3.84 ± 0.014; Mean SD) and therefore, highest bioaccessibility (55.7%) compared to the longer transit time of 160 minutes (0.81 ± 0.002; Mean SD) and (11.8%) for β-carotene concentration and bioaccessibility from a standard meal, respectively.DiscussionThe results suggest that gastric behaviour of the food determines the kinetics of bioaccessibility that may not result in low β-carotene release and ultimately low bioaccessibility from the embedded matrix.