Biokinetic Analysis Research Articles

Determination of organ doses in thyroid treatments with radioactive iodine by Monte Carlo simulation

I-131 is a radioisotope widely used in nuclear medicine for the treatment of pathologies such as thyroid cancer or hyperthyroidism. When I-131 is ingested, it rapidly accumulates in the thyroid gland, emitting radiation that affects the targeted thyroid tissue while also impacting other organs. To ensure patients receive the appropriate dose for desired therapeutic outcomes while minimizing the risk of adverse effects, accurate estimations of absorbed doses after the treatment is crucial. This study focuses on evaluating organ doses following I-131 pill administration. It leverages the recent High-Resolution Anthropomorphic Computational Phantom distributed by the International Commission on Radiological Protection (ICRP), known as the Mesh Type Reference Computational Phantom. Additionally, a biokinetic analysis of iodine is conducted using a Matlab-developed tool based on the ICRP compartment model for oral iodine administration. Furthermore, Monte Carlo simulation techniques employing the MCNP6.2 code have been used to examine the radiation transport within the phantom at various time points. Consequently, the study provides dose data for each affected organ throughout the treatment, demonstrating the suitability of this simulation methodology for conducting dosimetric investigations in thyroid treatment.

Improving photofermentative hydrogen productivity of photosynthetic bacteria using a formulated Fe and Mo metal supplemented lignocellulosic substrate

Strategy to improve single-stage photofermentative hydrogen productivity of photosynthetic bacteria (PSB) by efficient use a formulated lignocellulosic substrate through suitable supplement of iron and molybdenum as enhancers of microbial activity of R. palustris was proposed. The maximum hydrogen production rate of 48.1 ml h−1 L−1 was obtained using response surface methodology as the result of accelerated bioreaction of proton reduction under inoculum density of 118.1 mg L−1, Fe2+ of 13.2 mg L−1 and Mo6+ of 2.65 μg L−1. Biokinetic analysis revealed the enhanced microbial activities in biomass synthesis and H2 production. Suitable metal addition enabled PSB to act in whole as biocatalyst to facilitate assimilation of the formulated electron-rich carbon source from wheat straw through the efficient electron transfer needed for both cell growth and enzyme function of nitrogenase. Therefore, higher kinetic values of kc in 0.146 h−1 and Rm in 59.4 ml h−1 L−1, accompanied with improved performances of H2 yield in 1.56 mol mol−1 carbon and substrate degradation in 93.6% were attained.

Respirometric tests in a combined UASB-MBR system treating wastewater containing emerging contaminants at different OLRs and temperatures: Biokinetic analysis

This research focuses on the application of respirometric techniques to provide new insights into the biokinetic behaviour of bacterial species developed in an Upflow Anaerobic Sludge Blanked -UASB reactor combined with a membrane bioreactor -MBR, treating urban wastewater with emerging contaminants frequently found in this kind of effluents. The lab-scale pilot plant was operated at different metabolic and operational conditions by limiting the organic loading rate- OLR of the influent. In a first stage, the MBR was performed with suspended biomass, while in a second stage bio-supports were introduced to operate coexisting suspended and fixed biomass. From the results of the microscopic monitoring of sludge, it was concluded that the decrease in OLR resulted in a greater disintegration of the floc structure, more dispersed growth, and a low presence of inter-floccular bonds. However, no effect of toxicity or inhibition of microorganisms caused by the presence of emerging contaminants -ECs was determined. Kinetic modelling was carried out to study the behaviour of the system. The results showed a slowing down of biomass degradative capacity at low OLR stages and operating at low temperatures of mixed liquor. In addition, a decrease in oxygen consumption was observed with decreasing biodegradable substrate, resulting in lower degradation of organic matter. Mean values of specific oxygen uptake rate and heterotrophic biomass yield at low OLR were SOUR end = 1.49 and 1.15 mg O2· g MLVSS−1 h−1 and YH,MLSSV end = 0.48 and 0.28 mg MLVSS· mg COD−1substrate at stage 1 (suspended biomass) and stage 2 (suspended and supported biomass), respectively. From the analysis of the endogenous decomposition constant (kd), a higher cell lysis was determined operating with suspended biomass (kd = 0.03 d−1) in comparison to the operation coexisting suspended and supported biomass (kd = 0.01 d−1). Heterotrophic biomass yield values (YH, MLVSS = 0.48 ± 0.06, 0.40 ± 0.01 and 0.29 ± 0.01 mg MLVSS· mg COD−1substrate at high, medium and low OLR) showed lower sludge production at low OLR due to the influence of substrate limitation on cell growth.

Preemptive methodology determining operational parameters for mainstream PN: Evaluating biokinetics of three functional microbiome in seeding sludge

Chemical oxygen demand (COD)/N ratio is attracted as an alternative strategy selectively suppressing nitrite oxidizing bacteria (NOB) in mainstream partial nitritation (PN). We investigated a methodology that proper COD/N ratio is preemptively evaluated from seeding sludge through biokinetic analysis for three functional aerobic microbes. The COD/N ratio facilitating PN was preemptively determined as ≥3 from the biokinetic assay using seeding sludge, which was successfully verified in continuous bioreactors. Interestingly, the relative biokinetic properties of NOB in oxygen competition between aerobic microbes were the key indicators to achieve mainstream PN. Microbial community results show that some aerobic heterotrophic bacteria (AHB) became predominant at higher COD/N ratio conditions (≥3) with decreasing Nitrospira spp. In other words, the COD/N ratio, which could deteriorate the relative oxygen competition of NOB depending on the microbial community, could be determined preemptively. Our results could suggest that the proposed methodology can be helpful to provide operational guideline of mainstream PN.

Microaerophilic activated sludge system for ammonia retention from high-strength nitrogenous wastewater: Biokinetics and mathematical modeling

It is crucial to shift from conventional ammonia removal to recovery to solve environmental problems and resource scarcity. Recovering ammonia from high-strength nitrogenous wastewater can simultaneously save the energy and cost involved in ammonia oxidation, produce ammonia without CO2 emissions, and prevent N2O emissions. A technology for concentrating and recovering ammonia by retrofitting a conventional activated sludge (CAS) system is promising but faces significant challenges in oxidizing organic carbon but not ammonia in wastewater. This study employed biokinetic analysis and mathematical modeling to comprehensively assess the operation and effectiveness of a microaerophilic activated sludge (MAS) system for simultaneously removing chemical oxygen demand (COD) and retaining ammonia. We show that heterotrophic bacteria (HB) in the MAS system had higher maximum specific growth rate (µHB), biomass yield coefficient (YHB), and decay coefficient (bHB) but lower affinities for oxygen and COD than HB in CAS. Simulations using the developed model demonstrated that COD removal efficiencies of > 90%, ammonia retention efficiencies of > 90%, and low N2O emission factors (N2OEF) of < 0.01% can be achieved at solids retention times (SRTs) of 3–50 d, hydraulic retention times (HRTs) of 0.1–1 d, and a volumetric oxygen transfer coefficient (KLa) of (24.58 ± 0.30)HRT−1. The combination of the biokinetics and mathematical modeling revealed the favorable MAS operating conditions allowing efficient ammonia retention and COD removal, which paves the way for turning a CAS system into a MAS system by retrofitting the configuration without high capital expenditures, requiring future intensive study.

Current trends in the biokinetic analysis of the foot and ankle

Although the importance of studying the anatomy of structures of the ankle and foot joints is fundamental, evidence points to a low correlation between static and dynamic measurements; this could represent a problem in the study of the functioning of the ankle and foot during daily activities. The aim of the present study is to review the classic knowledge on ankle and foot biomechanics and present new concepts of functional biomechanics (3-dimensional biokinetic analysis) in order to clarify their clinical applications in assisting diagnostic and/or treatment decisions. For this, we performed a literature review and divided the article into 6 sections: (1) functional biomechanics of the ankle and foot; (2) dynamic joint stability; (3) functional stability mechanisms of the foot; (4) functional stability mechanisms of the ankle; (5) gait and running biokinetics; (6) the role of proximal joints in ankle and foot movement. At the end of this article, the reader should be able to understand how the 3-dimensional biokinetic analysis of the ankle and foot can contribute along with imaging examinations to the clinical setting, thus allowing the construction of a more complete profile of the patient. Such information could enable the identification of weaknesses and the implementation of objective interventions for each patient. Level of Evidence V; Prognostic Studies; Expert Opinion.

Novel composite gel beads for the immobilization of ammonia-oxidizing bacteria: Fabrication, characterization, and biokinetic analysis

Novel composite gel beads that entrap ammonia-oxidizing bacteria (AOB) were developed for wastewater treatment. The AOB-entrapping composite gel beads, which were monodispersed and millimeter-sized, were produced by a method that combined suspension-gelation with sedimentation polymerization. This method involves the preparation of calcium alginate microcapsules, which contain AOB, by electrostatic atomization and free radical polymerization of droplets of a pre-gel aqueous suspension containing microcapsules during their descent into silicone oil. AOB-entrapping non-porous gel beads, without the microcapsules, were also prepared as a control. The AOB entrapped in both the composite and non-porous gels were grown in a continuous stirred tank reactor fed with synthetic inorganic nitrogenous wastewater. The AOB-entrapping gels successfully catalyzed ammonia oxidation. The kinetics of the reaction were analyzed using the Haldane model with inhibition by a substrate.

Biokinetic Analysis and Metabolic Fate of 2,4-D in 2,4-D-Resistant Soybean (Glycine max).

The Enlist weed control system allows the use of 2,4-D in soybean but slight necrosis in treated leaves may be observed in the field. The objectives of this research were to measure and compare uptake, translocation, and metabolism of 2,4-D in Enlist (E, resistant) and non-AAD-12 transformed (NT, sensitive) soybeans. The adjuvant from the Enlist Duo herbicide formulation (ADJ) increased 2,4-D uptake (36%) and displayed the fastest rate of uptake (U50= 0.2 h) among treatments. E soybean demonstrated a faster rate of 2,4-D metabolism (M50= 0.2 h) compared to NT soybean, but glyphosate did not affect 2,4-D metabolism. Metabolites of 2,4-D in E soybean were qualitatively different than NT. Applying 2,4-D-ethylhexyl ester instead of 2,4-D choline (a quaternary ammonium salt) eliminated visual injury to E soybean, likely due to the time required for initial de-esterification and bioactivation. Excessive 2,4-D acid concentrations in E soybean resulting from ADJ-increased uptake may significantly contribute to foliar injury.

Biokinetics of Aerosolized Liposomal Ciclosporin A in Human Lung Cells In Vitro Using an Air-Liquid Cell Interface Exposure System.

Inhalation of aerosolized drugs is a promising route for noninvasive targeted drug delivery to the lung. Nanocarrier systems such as liposomes have been explored for inhalation therapy opening new avenues, including stabilization of nonsoluble drugs (e.g., Ciclosporin A [CsA]) and controlled release. The biokinetic behavior of the immunosuppressive drug CsA encapsulated in liposomes (L-CsA) at the lung epithelial barrier was studied in vitro. Human lung epithelial cells (alveolar A549 and bronchial 16HBE14o- epithelial cells) were exposed to aerosolized L-CsA at the air-liquid interface (ALI) using a dose-controlled air-liquid interface cell exposure (ALICE) system and the temporal profile of the L-CsA dose in the apical, basal, and cell compartment was monitored up to 24 hours. Aerosolization of different volumes of L-CsA solution with the ALICE resulted in dose-controlled, spatially uniform, and reproducible L-CsA delivery. Cell viability at 24 hours postexposure was not impaired and immunofluorescence staining revealed the typical epithelial cell morphology in control as well as in L-CsA-exposed cells. The (pro-)inflammatory interleukin-8 levels were not elevated under any condition. The biokinetic analysis revealed that both cell types formed a tight, but imperfect, barrier for L-CsA resulting in initially high transbarrier L-CsA transport rates, which ceased after about 4 hours. Although substantial transbarrier L-CsA transport was observed for both cell types, respectively, a 150-fold higher L-CsA concentration was established in the apical and cell compared to the basal compartment. Most importantly, for pulmonary drug targeting, a high cellular L-CsA dose level (20%-25% of the delivered dose) was obtained rapidly (<1 hour) and maintained for at least 24 hours. The ALICE system combined with lung epithelial cells cultured at the ALI offers a reliable and relevant in vitro platform technology to study the effects of inhalable substances such as L-CsA under biomimetic conditions.

Ammonium removal from coking wastewater in a pilot‐scale two‐stage aerobic biofilm system: Biokinetic analysis

AbstractA novel four‐stage pilot‐scale anaerobic/anoxic/oxic/oxic (A2/O2) biofilm process was successfully developed to treat coking wastewater with high ammonium loading. In this study, three different dynamical models including the first‐order substrate removal model, the Monod‐biological contact oxidation (Monod‐BCO) model, and the modified Stover‐Kincannon model were particularly applied to analyze kinetics of ammonium removal in a two‐step aerobic stage. For the O1 reactor, all models were appropriate for describing ammonium removal and the correlation coefficients of first‐order substrate removal model, BCO model, and modified Stover‐Kincannon model were 0.8974, 0.9210, and 0.9726, respectively. The model verification indicated that the modified Stover‐Kincannon model was slightly more applicable to predict ammonium removal in the O1 reactor. It was demonstrated that the maximum removal rate of ammonium was 0.208 kg/(m3 · d) by the Stover‐Kincannon model. For the O2 reactor, the modified Stover‐Kincannon model turned out to be the best fitting kinetic model for ammonium removal compared to the first‐order substrate removal model (R2 = 0.1556) and Monod‐BCO model (R2 = 0.5022). The maximum ammonium conversion rate (Um2‐O2) by the modified Stover‐Kincannon model was 1.180 kg/(m3 · d), while saturation rate constant k3‐O2 was 1.221 kg/(m3 · d). Furthermore, the determination coefficient between measured and predicted values obtained by the modified Stover‐Kincannon model was quite high (R2 = 0.9788) in the O2 process and a lower average residual square (6.60 × 10−6) was also obtained. The results of kinetic studies by the Stover‐Kincannon model can predict ammonia removal efficiency well in two‐step aerobic biofilm reactors of a coking wastewater treatment combined system.

Depth investigation of rapid sand filters for drinking water production reveals strong stratification in nitrification biokinetic behavior

The biokinetic behavior of NH4+ removal was investigated at different depths of a rapid sand filter treating groundwater for drinking water preparation. Filter materials from the top, middle and bottom layers of a full-scale filter were exposed to various controlled NH4+ loadings in a continuous-flow lab-scale assay. NH4+ removal capacity, estimated from short term loading up-shifts, was at least 10 times higher in the top than in the middle and bottom filter layers, consistent with the stratification of Ammonium Oxidizing Bacteria (AOB). AOB density increased consistently with the NH4+ removal rate, indicating their primarily role in nitrification under the imposed experimental conditions. The maximum AOB cell specific NH4+ removal rate observed at the bottom was at least 3 times lower compared to the top and middle layers. Additionally, a significant up-shift capacity (4.6 and 3.5 times) was displayed from the top and middle layers, but not from the bottom layer at increased loading conditions. Hence, AOB with different physiological responses were active at the different depths. The biokinetic analysis predicted that despite the low NH4+ removal capacity at the bottom layer, the entire filter is able to cope with a 4-fold instantaneous loading increase without compromising the effluent NH4+. Ultimately, this filter up-shift capacity was limited by the density of AOB and their biokinetic behavior, both of which were strongly stratified.

Bio-Kinetic Analysis of Tannery and Sago Effluents Treated in UASB and HUASB Reactor

The present study is related to treatment of tannery and sago wastewater in up flow anaerobic sludge blanket reactor and hybrid reactor. The effectiveness of the biological treatment of wastewater involves appropriate microorganisms. COD was reduced to 91.67% and 92.38% in UASB reactor and HUASB reactor. Likewise the BOD was reduced to 83.73% and 90.96% in UASB and HUASB respectively at an HRT of 45 h. The reactor was operated at an OLR of 4.210 mg COD/min L. Various Bio-kinetic models were applied to data obtained from the experimental studies in batch operated UASB and HUASB reactors. Treatment efficiencies were investigated at different hydraulic retention times. Second order models were found to be the best fit for all the effluents treated in both the reactor. The second order model showed the fitness with regression coefficient more than 0.91.

Biokinetic analysis of tissue boron (10B) concentrations of glioma patients treated with BNCT in Finland

A total of 98 patients with glioma were treated with BPA-F-mediated boron neutron capture therapy (BNCT) in Finland from 1999 to 2011. Thirty-nine (40%) had undergone surgery for newly diagnosed glioblastoma and 59 (60%) had malignant glioma recurrence after surgery. In this study we applied a closed 3-compartment model based on dynamic 18F-BPA-PET studies to estimate the BPA-F concentrations in the tumor and the normal brain with time. Altogether 22 patients with recurrent glioma, treated within the context of a clinical trial, were evaluated using their individual measured whole blood 10B concentrations as an input to the model. The delivered radiation doses to tumor and the normal brain were recalculated based on the modeled 10B concentrations in the tissues during neutron irradiation. The model predicts from −7% to +29% (average, +11%) change in the average tumor doses as compared with the previously estimated doses, and from 17% to 61% (average, 36%) higher average normal brain doses than previously estimated due to the non-constant tumor-to-blood concentration ratios and considerably higher estimated 10B concentrations in the brain at the time of neutron irradiation.

Mechanism of cisplatin proximal tubule toxicity revealed by integrating transcriptomics, proteomics, metabolomics and biokinetics

Cisplatin is one of the most widely used chemotherapeutic agents for the treatment of solid tumours. The major dose-limiting factor is nephrotoxicity, in particular in the proximal tubule. Here, we use an integrated omics approach, including transcriptomics, proteomics and metabolomics coupled to biokinetics to identify cell stress response pathways induced by cisplatin. The human renal proximal tubular cell line RPTEC/TERT1 was treated with sub-cytotoxic concentrations of cisplatin (0.5 and 2μM) in a daily repeat dose treating regime for up to 14days. Biokinetic analysis showed that cisplatin was taken up from the basolateral compartment, transported to the apical compartment, and accumulated in cells over time. This is in line with basolateral uptake of cisplatin via organic cation transporter 2 and bioactivation via gamma-glutamyl transpeptidase located on the apical side of proximal tubular cells. Cisplatin affected several pathways including, p53 signalling, Nrf2 mediated oxidative stress response, mitochondrial processes, mTOR and AMPK signalling. In addition, we identified novel pathways changed by cisplatin, including eIF2 signalling, actin nucleation via the ARP/WASP complex and regulation of cell polarization. In conclusion, using an integrated omic approach together with biokinetics we have identified both novel and established mechanisms of cisplatin toxicity.

Biokinetic analysis code development and applications to visualise the distribution of intake activity

Measurements for internal dose assessment are required to be conducted based on the distribution of radionuclides in the body, which may change depending on the lapsed time. In this study, a biokinetic analysis code, which can be used in practical radiation control is developed, and the results of (60)Co and (137)Cs biokinetics are visualised as examples by drawing the depositions for each organ and tissue in a figure of the body as a function of lapsed time. In addition, based on visualised biokinetics, precautions for in vivo measurements are also discussed. These discussions led to the conclusion that the information of visualised biokinetics is useful for actual measurements in practical radiation control.

Non-Negative Matrix Factorization Based Input Function Extraction for Mouse Imaging in Small Animal PET ? Comparison with Arterial Blood Sampling and Factor Analysis

Objectives: Retrieving the accurate time-tracer activity concentration curve of the blood (arterial input function) is mandatory for performing bio kinetic model analysis of dynamic PET data. Especially in small rodents, gathering the input function remains an active area of research as no generally applicable solution was found so far. While surgically catheterizing blood vessels of rodents is possible, it is labour intensive and time resolution of blood sampling is restricted due to the limited amount of overall blood and the procedure of blood withdrawal itself. Obtaining the input function from the PET images themselves seems thus to be favourable, but suffers from several factors, one of them being spill-in of adjacent tissues. Particularly in mice and for [18F]FDG, the spill-in complicates using the time-activity curve (TAC) from a region of interest (ROI) over the left ventricle (LV) because the signal of the ROI contains contributions from both, myocardial uptake as well as arterial blood activity. We propose non-negative matrix factorization (NMF) as an image based algorithm for separating myocardial tracer concentration from the blood input function. The aim of this study was to evaluate the potential of NMF as an image based algorithm for retrieving the input function by comparison with blood sampling and Factor Analysis (FA). Method: The femoral arteries of eight mice were surgically catheterized. With the injection of [18F]FDG, a 60 minute PET scan was started during which arterial blood samples were manually drawn from the catheter. For analysis, NMF and FA were performed in a ROI placed over the LV. The NMF algorithm shares similarities with principal component analysis and FA, the advantage over the later two being its non-negativity constraint. For normalization of the NMF extracted curve, the peak value of tracer activity in an early image of the LV and a late blood sample was used. The normalized NMF curve was visually compared to the TAC retrieved from the blood samples and to the FA retrieved TAC. For a quantitative comparison of performance, Pearson correlation and square-root of sum of squares (RSS) between NMF/FA and blood sampling curves was calculated. Results: TAC based on NMF, FA and arterial blood samples were obtained and compared in all 8 mice. The NMF derived curves described the blood sampling based curves visually significantly better than FA. Pearson correlation between NMF and blood sampling curves ranged from 0.21 to 0.92 with an average of 0.69. Pearson correlation for FA ranged from 0.46 to 0.81 with an average of 0.65. Mean RSS was 2.70E + 006 for NMF and 3.40E + 006 for FA. Conclusion: In the examined parameters, visual accordance, Pearson correlation and RSS, NMF performs superior to FA and seems to be a promising method for the extraction of the input function from PET images of small rodents without the need for arterial blood sampling.

Bio-kinetic analysis on treatment of textile dye wastewater using anaerobic batch reactor

An anaerobic digestion technique was applied to textile dye wastewater aiming at the colour and COD removal. Pet bottles of 5 L capacity were used as reactor which contains methanogenic sludge of half a liter capacity which was used for the treatment of combined synthetic textile dye and starch wastewater at different mixing ratios of 20:80, 30:70, 40:60, 50:50 and 60:40 with initial COD concentrations as 3520, 3440, 3360, 3264 and 3144 mg L(-1), respectively. The reactor was maintained at room temperature (30±3°C) with initial pH of 7. The maximum COD and colour removal were 81.0% and 87.3% at an optimum mixing ratio of 30:70 of textile dye and starch wastewaters. Both Monod's and Haldane's models were adopted in this study. The kinetic constants of cell growth under Haldane's model were satisfactory when compared to Monod's model. The kinetic constants obtained by Haldane's model were found to be in the range of μmax=0.037-0.146 h(-1), Ks=651.04-1372.88 mg L(-1) and Ki=5681.81-18727.59 mg L(-1).

Distribution and biokinetic analysis of 210Pb and 210Po in poultry due to ingestion of dicalcium phosphate

Dicalcium phosphate (DCP) is used as a calcium supplement for food producing animals (i.e., cattle, poultry and pig). When DCP is produced via wet acid digestion of the phosphate rock and depending on the acid used in the industrial process, the final product can result in enhanced 210Pb and 210Po specific activities (∼ 2000 Bq·kg − 1). Both 210Pb and 210Po are of great interest because their contribution to the dose received by ingestion is potentially large. The aims of this work are to examine the accumulation of 210Pb and 210Po in chicken tissues during the first 42 days of life and to build a suitable single-compartment biokinetic model to understand the behavior of both radionuclides within the entire animal using the experimental results. Three commercial corn-soybean-based diets containing different amounts and sources of DCP were fed to broilers during a period of 42 days. The results show that diets containing enhanced concentrations of 210Pb and 210Po lead to larger specific accumulation in broiler tissues compared to the blank diet. Radionuclides do not accumulate homogeneously within the animal body: 210Pb follows the calcium pathways to some extent and accumulates largely in bones, while 210Po accumulates to a large extent in liver and kidneys. However, the total amount of radionuclide accumulation in tissues is small compared to the amounts excreted in feces. The single-compartment non-linear biokinetic model proposed here for 210Pb and 210Po in the whole animal takes into account the size evolution and is self-consistent in that no fitting parameterization of intake and excretions rates is required.

Biokinetics of buccal spray insulin in patients with type 1 diabetes

Objective To evaluate the metabolic effect of buccal spray insulin compared with subcutaneous regular insulin in patients with type 1 diabetes. Research Design and Methods This study compared plasma glucose, insulin, and C-peptide levels in 18 patients with type 1 diabetes treated with subcutaneous regular or buccal spray insulin on 2 consecutive mornings. On day 1, patients were treated with their usual subcutaneous regular insulin regimens. On day 2, patients received buccal spray insulin. In the morning of both days 1 and 2, patients received a standard meal of 630 kJ. No intermediate or long-acting insulin was administered to patients on the morning of the test. Blood samples were collected for up to 4 hours for biokinetic analysis. In a subset of 3 patients, premeal buccal spray insulin was administered for 2 entire consecutive days. In these patients, glucose levels were monitored using the glucose sensor monitoring system. Results Overall, there were no statistically significant differences in glucose, insulin, or C-peptide levels measured after administration of subcutaneous vs buccal spray insulin. However, at 90 and 120 minutes after subcutaneous regular insulin administration, significantly higher insulin levels and more prolonged hypoglycemic effect were detected compared with buccal spray insulin administration. In the 3 patients who received 1 day of regular and 2 entire days of buccal spray insulin, no significant differences were observed in glucose levels during the 3 days of glucose sensor monitoring. Conclusions Insulin administered via the buccal spray formulation is as effective as the subcutaneous route in lowering blood glucose levels.

Biokinetic analysis of vitamin absorption and disposition in humans

Publisher Summary This chapter discusses the biokinetic analysis of vitamin absorption and disposition in humans. Following the determination of vitamin baseline concentrations in body fluids and the administration of the vitamin test dose, blood and urine samples are repeatedly taken to allow kinetic analysis of the vitamin concentration-versus-time curves. The duration of sampling is determined by the compliance of the subjects to obey the study protocol and the requirement of a sufficient number of data points during the terminal phase of vitamin disposition. Favorably, vitamin baseline concentrations as observed before the administration of the vitamin test dose are reached again when the trial is terminated. The achievement of baseline levels is mainly determined by the disposition characteristics of the vitamin. Intravenously (i.v.) administered pyridoxine hydrochloride has a plasma half-life of ∼0.11 hr. The terminal half-life of its metabolite pyridoxal 5'-phosphate is 31.5 hours.