Development of an Innovative Berberine Food-Grade Formulation with an Ameliorated Absorption: In Vitro Evidence Confirmed by Healthy Human Volunteers Pharmacokinetic Study

Objective. To evaluate in vitro solubility, bioaccessibility, and cytotoxic profile, together with a pharmacokinetic profile by oral administration to healthy volunteers of a novel food-grade berberine formulation (BBR-PP, i.e., berberine Phytosome®). Results. An in vitro increase of solubility in simulated gastric and intestinal fluids and an improved bioaccessibility at intestinal level along with a lower cytotoxicity with respect to berberine were observed with BBR-PP. The pharmacokinetic profile of the oral administration to healthy volunteers confirmed that berberine Phytosome® significantly ameliorated berberine absorption, in comparison to unformulated berberine, without any observed side effects. The berberine plasma concentrations observed with both doses of BBR-PP were significantly higher than those seen after unformulated berberine administration, starting from 45 min (free berberine) and 30 min (total berberine). Furthermore, BBR-PP improved berberine bioavailability (AUC) was significantly higher, around 10 times on molar basis and with observed dose linearity, compared to the unformulated berberine. Conclusion. These findings open new perspectives on the use of this healthy berberine formulation in metabolic discomforts.

Re-Evaluation of Chromium Doped Alumina for Dosimetric Applications

Many medical examinations involve ionizing radiation. Although the range of available dosimeters is rather wide, their linearity and chemical stability are limited. Recently, there has been a growing interest in new, improved dosimetric materials for emerging applications in medicine and other fields, such as sterilisation of consumer goods and medical instruments, irradiation of seeds, chemical agents and others.One of the classical dosimeters is carbon-doped alumina (Al2O3:C) – a well-established and widely used material for personal and industrial dosimeter with a range of great properties, such as high sensitivity, wide linearity range and relative ease of production and handling. However, the demand for reliable dosimeters in a high-dose range is still only partially fulfilled, and alumina doped with chromium ions (Al2O3:Cr) can be a promising candidate.In this study, we explored alumina doped with chromium porous microparticles synthesized with a sol-gel method as a possible high dose dosimeter and evaluated its thermostimulated luminescence signal, dose response with two irradiation sources and measured long-time fading. It was found that although the TSL signal was quite complex (consisting of two main peaks above room temperature) and the long-term fading was significant (around 50 % in the span of 30 days), with sufficient optimisation the material could be used as a high-dose dosimeter for X-ray and beta irradiation. Wide high dose linearity range, physical and chemical characteristics, as well as low production costs and ease of synthesis make chromium (III) doped alumina a compelling candidate for applicability in various medical and industry fields.

Characterization of Small Dosimeters Used for Measurement of Eye Lens Dose for Medical Staff during Fluoroscopic Examination

This study aimed to evaluate the property of small dosimeters used for measuring eye lens doses for medical staff during fluoroscopic examination. Dose linearity, energy dependence, and directional dependence of scattered X-rays were evaluated for small radiophotoluminescence glass dosimeters (RPLDs), those with a tin filter (Sn-RPLDs), and small optically stimulated luminescence dosimeters (OSLDs). These dosimeters were pasted on radioprotective glasses, and accumulated air kerma was obtained after irradiating the X-rays to a patient phantom. Strong correlations existed between fluoroscopic time and accumulated air kerma in all types of dosimeters. The energy dependence of Sn-RPLD and OSLD was smaller than that of RPLD. The relative dose value of the OSLD gradually decreased as the angle of the OSLD against the scattered X-rays was larger or lower than the right angle in the horizontal direction. The ranges of relative dose values of RPLD and Sn-RPLD were larger than that of OSLD in the vertical direction. The OSLDs showed lower doses than the RPLDs and Sn-RPLDs, especially on the right side of the radioprotective glasses. These results showed that RPLDs, Sn-RPLDs, and OSLDs had different dosimeter properties, and influence measured eye lens doses for the physician, especially on the opposite side of the patient.

Development of Novel Real-Time Radiation Systems Using 4-Channel Sensors

Radiation-related tissue injuries after medical radiation procedures, such as fluoroscopically guided intervention (FGI), have been reported in patients. Real-time monitoring of medical radiation exposure administered to patients during FGI is important to avoid such tissue injuries. In our previous study, we reported a novel (prototype) real-time radiation system for FGI. However, the prototype sensor indicated low sensitivity to radiation exposure from the side and back, although it had high-quality fundamental characteristics. Therefore, we developed a novel 4-channel sensor with modified shape and size than the previous sensor, and evaluated the basic performance (i.e., measured the energy, dose linearity, dose rate, and angular dependence) of the novel and previous sensors. Both sensors of our real-time dosimeter system demonstrated the low energy dependence, excellent dose linearity (R2 = 1.0000), and good dose rate dependence (i.e., within 5% statistical difference). Besides, the sensitivity of 0° ± 180° in the horizontal and vertical directions was almost 100% sensitivity for the new sensor, which significantly improved the angular dependence. Moreover, the novel dosimeter exerted less influence on X-ray images (fluoroscopy) than other sensors because of modifying a small shape and size. Therefore, the developed dosimeter system is expected to be useful for measuring the exposure of patients to radiation doses during FGI procedures.

Feasibility study on a novel tiny dosimeter using a barium titanate capacitor

ABSTRACT In our laboratory we have confirmed that the capacitance of barium titanate-based capacitors changes due to radiation. Since a commercially available capacitor is very small and inexpensive, it may be used as a multidimensional dose meter in which a large number of capacitor elements are arranged, or may be embedded in the body and used as an in-vivo dose meter. In this study we examined the usefulness of a dosimeter using the capacitance change of a barium titanate capacitor. As a basic property, it was confirmed that the dose linearity was good. With regard to dose rate characteristics and response to fractionated irradiation, capacitance change due to aging affects measurement accuracy, but online measurement of capacitance change immediately before irradiation can be performed to correct aging effects during irradiation. By doing this, we confirmed that the dose rate characteristics and the response to fractionated radiation are improved.

O20 Dose-linearity of the pharmacokinetics of an intravenous [14C]midazolam microdose in children

BackgroundDrug disposition in children may vary from adults due to age-related variation in drug metabolism, but paediatric pharmacokinetic (PK) studies are challenging. Microdose studies present an innovation to study PK in paediatrics, and can only be used when the PK of a microdose are dose-linear to a therapeutic dose. We aimed to assess dose-linearity of [14C]midazolam (MDZ), a marker for the activity of the developmentally regulated CYP3A enzyme, by comparing the PK of an intravenous (IV) [14C]MDZ microtracer given simultaneously with therapeutic MDZ, with the PK of a single IV [14C]MDZ microdose.MethodsPreterm to 2-year-old infants admitted to the intensive care unit received [14C]MDZ IV either as a microtracer during therapeutic MDZ infusion or as an isolated microdose. Dense blood sampling was done up to 36 hours after dosing. Plasma concentrations of [14C]MDZ and [14C]1-OH-MDZ were determined by accelerator mass spectrometry. A population PK model was developed with NONMEM 7.4 to study whether there was a difference in the PK of the microtracer versus those of a microdose [14C]MDZ.ResultsOf fifteen children (median gestational age 39.4 [range 23.9–41.4] weeks, postnatal age 11.4 [0.6–49.1] weeks), nine received a microdose and six a microtracer [14C]MDZ (111 Bq/kg; 37.6 ng/kg). In a two-compartment PK model, bodyweight was the most significant covariate for volume of distribution. There was no statistically significant difference in any PK parameter between the [14C]MDZ microdose or microtracer, suggesting the PK of MDZ to be linear within the range of the therapeutic doses and microdoses.ConclusionOur data supports the dose-linearity of an IV [14C]MDZ microdose in children, thus a [14C]MDZ microdosing approach can be used to study developmental changes in hepatic CYP3A activity.Disclosure(s)This project was funded by the ZonMw ERA-NET PRIOMEDCHILD programme (projectnumber 113205022). * both authors contributed equally