scholarly journals Construction of Windows for Pharmacokinetic Sampling

2021 ◽  
Vol 50 (5) ◽  
pp. 23-37
Author(s):  
M. Iftakhar Alam ◽  
Nigar Sultana

This paper describes a method for the construction of pharmacokinetic sampling windows so that they are around the $D$-optimum time points. Here we consider the situation where a pharmacokinetic (PK) study is accompanied by a dose-finding study in phase I clinical trial. The D-optimal criterion is often used to determine the optimal time for collecting blood samples so that they provide maximum information regarding the population PK parameters. However, collecting blood samples at the D-optimal time points is often difficult. Instead, the sampling time point chosen from a suitable time interval or window can ease the process. The proposed method is conceptually simple and considers the average value and standard deviation of D-optimal time points up to create sampling windows. Random time points can be chosen from these windows then to collect blood samples from the next cohort. The nonlinear random-effects model has been used to model the PK data. Also, we employ the continual reassessment method for dose allocation to the patients. Comparisons of the accuracy and precision for the PK parameter estimates obtained at the D-optimal and random time points are also presented. The results are convincing enough to suggest the proposed method as a useful tool for blood sample collection.

2017 ◽  
Vol 27 (3) ◽  
pp. 264-270 ◽  
Author(s):  
Rieneke Terink ◽  
Michiel G.J. Balvers ◽  
Maria T. Hopman ◽  
Renger F. Witkamp ◽  
Marco Mensink ◽  
...  

Magnesium is essential for optimal sport performance, generating an interest to monitor its status in athletes. However, before measuring magnesium status in blood could become routine, more insight into its diurnal fluctuations and effects of exercise itself is necessary. Therefore, we measured the effect of an acute bout of exercise on ionized (iMg) and total plasma magnesium (tMg) in blood obtained from 18 healthy well-trained endurance athletes (age, 31.1 ± 8.1 yr.; VO2max, 50.9 ± 7.5 ml/kg/min) at multiple time points, and compared this with a resting situation. At both days, 7 blood samples were taken at set time points (8:30 fasted, 11:00, 12:30, 13:30, 15:00, 16:00, 18:30). The control day was included to correct for a putative diurnal fluctuation of magnesium. During the exercise day, athletes performed a 90 min bicycle ergometer test (70% VO2max) between 11:00 and 12:30. Whole blood samples were analyzed for iMg and plasma for tMg concentrations. Both concentrations decreased significantly after exercise (0.52 ± 0.04–0.45 ± 0.03 mmol/L and 0.81 ± 0.07–0.73 ± 0.06 mmol/L, respectively, p < .001) while no significant decline was observed during that time-interval on control days. Both, iMg and tMg, returned to baseline, on average, 2.5 hr after exercise. These findings suggest that timing of blood sampling to analyze Mg status is important. Additional research is needed to establish the recovery time after different types of exercise to come to a general advice regarding the timing of magnesium status assessment in practice.


2020 ◽  
Vol 7 ◽  
Author(s):  
Patrick S. Harty ◽  
Hannah A. Zabriskie ◽  
Richard A. Stecker ◽  
Brad S. Currier ◽  
Grant M. Tinsley ◽  
...  

Little is known about the optimal time to consume caffeine prior to exercise to maximize the ergogenic benefits of the substance.Purpose: To determine the optimal pre-exercise time interval to consume caffeine to improve lower-body muscular performance. A secondary aim was to identify the presence of any sex differences in responses to timed caffeine administration.Methods: Healthy, resistance-trained males (n = 18; Mean±SD; Age: 25.1 ± 5.7 years; Height: 178.4 ± 7.1 cm; Body mass: 91.3 ± 13.5 kg; Percent body fat: 20.7 ± 5.2; Average caffeine consumption: 146.6 ± 100.3 mg/day) and females (n = 11; Mean ± SD; Age: 20.1 ± 1.6 years; Height: 165.0 ± 8.8 cm; Body mass: 65.8 ± 10.0 kg; Percent bodyfat: 25.8 ± 4.2; Average caffeine consumption: 111.8 ± 91.7 mg/day) participated in this investigation. In a randomized, double-blind, placebo-controlled, crossover fashion, participants consumed 6 mg·kg−1 caffeine or placebo solution at three time points: 2 h prior (2H), 1 h prior (1H), or 30 min prior (30M) to exercise testing. During three visits, caffeine was randomly administered at one time point, and placebo was administered at the other two time points. During one visit, placebo was administered at all three time points. Next, participants performed isometric mid-thigh pulls (IMTP), countermovement vertical jumps (CMVJ), and isometric/isokinetic knee extensor testing (ISO/ISOK).Results: Caffeine administered at 1H significantly improved absolute CMVJ and ISO performance relative to placebo. Mean CMVJ jump height was significantly higher during 1H compared to 30M. However, only caffeine administered at 30M significantly improved absolute measures of isokinetic performance. Analysis of the pooled caffeine conditions revealed that muscular performance was more consistently augmented by caffeine in males compared to females.Conclusions: Pre-exercise caffeine timing significantly modulated participant responses to the substance, with 1H exerting the most consistent ergogenic benefits relative to other time points, particularly compared to 2H. Male participants were found to respond more consistently to caffeine compared to female participants. These results suggest that active individuals can maximize the ergogenic effects of caffeine by consuming the substance ~1 h prior to the point when peak muscular performance is desired.


2017 ◽  
Vol 920 (2) ◽  
pp. 57-60
Author(s):  
F.E. Guliyeva

The study of results of relevant works on remote sensing of forests has shown that the known methods of remote estimation of forest cuts and growth don’t allow to calculate the objective average value of forests cut volume during the fixed time period. The existing mathematical estimates are not monotonous and make it possible to estimate primitively the scale of cutting by computing the ratio of data in two fixed time points. In the article the extreme properties of the considered estimates for deforestation and reforestation models are researched. The extreme features of integrated averaged values of given estimates upon limitations applied on variables, characterizing the deforestation and reforestation processes are studied. The integrated parameter, making it possible to calculate the averaged value of estimates of forest cutting, computed for all fixed time period with a fixed step is suggested. It is shown mathematically that the given estimate has a monotonous feature in regard of value of given time interval and make it possible to evaluate objectively the scales of forest cutting.


Animals ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 926
Author(s):  
Daniela M. Meléndez ◽  
Sonia Marti ◽  
Luigi Faucitano ◽  
Derek B. Haley ◽  
Timothy D. Schwinghamer ◽  
...  

Lactate is a product of anaerobic glycolysis, used in animal research as an indicator of muscle fatigue. Therefore, it has been used as an indicator of cattle response to long distance transportation. The aim of this study was to assess the relationship of L-lactate concentrations measured using a Lactate Scout+ analyzer and a traditional lactate assay colorimetric kit. Blood samples were collected by venipuncture from 96 steers (Black or Red Angus × Hereford/Simmental and Black or Red Angus × Charolais; 247 ± 38.2 kg BW) prior to loading (LO1) and after 36 h of transport, and prior to reloading and after an additional 4 h of road transportation, and on d 1, 2, 3, 5, 14, and 28 after transport. The Lactate Scout+ analyzer strip was dipped in blood at the time of sampling, while blood samples were collected into sodium fluoride tubes for use in the colorimetric analysis. Pearson correlations were calculated to assess the strength of the relationship between the experimental methods for the quantification of L-lactate concentrations. The magnitude and direction of the correlation, and the level of statistical significance varied over the observed time points, ranging from r = −0.03 (p = 0.75; LO1) to r = 0.75 (p < 0.0001; d 3). The correlation for the pooled data was weak but statistically significant (r = 0.33, p < 0.0001). Based on the low magnitude of the correlation due to variability across sampling time points in this study, the Lactate Scout+ analyzer is not a suitable alternative to a lab-based assay (considered the gold standard) for measuring L-lactate in transported cattle.


2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 296-297
Author(s):  
Daniela M Meléndez ◽  
Sonia Marti ◽  
Luigi Faucitano ◽  
Derek B Haley ◽  
Timothy D Schwinghamer ◽  
...  

Abstract Blood metabolites are used to assess a variety of animal conditions for veterinary diagnosis and research. Concentration of metabolites in blood can be measured using a commercially-available lab-based assay or in real-time using a handheld device developed to be more time- and cost-effective than the lab-based method. Lactate is a product of anaerobic glycolysis, used in animal research as an indicator of muscle fatigue. Therefore, it has been used as an indicator of cattle response to long distance transportation. The aim of this study was to assess the relationship of L-lactate concentrations measured using a Lactate Scout+ analyzer (Lactate Scout, EFK Diagnostics, Barleben, Germany) and a lactate assay colorimetric kit (Lactate Assay Kit, Cell Biolabs Inc., San Diego, CA). Blood samples were collected by venipuncture from 96 steers (245 ± 35.7 kg BW) prior to (L1) and after 36 h, and prior to and after an additional 4 h of road transportation, and on d 1, 2, 3, 5, 14, and 28 after transport. The Lactate Scout+ analyzer strip was dipped in blood at the time of sampling, while blood samples were collected into sodium fluoride tubes for use in colorimetric analysis. Pearson correlations were calculated to determine the relationship between the experimental methods for the quantification of L-lactate concentrations. The strengths and levels of statistical significance of the correlation varied over the observed time points, r = -0.03, P = 0.75 (L1) to r = 0.75, P = &lt; 0.0001 (d 3). The correlation for the pooled data was weak but statistically significant (r = 0.33, P &lt; 0.001). Based on the experimental results, the Lactate Scout+ analyzer is not a suitable alternative to a lab-based assay for measuring L-lactate in transported cattle, due to variability across sampling time points and weak correlation with the traditional enzymatic method.


Author(s):  
Sebastian Hacker ◽  
Thomas Reichel ◽  
Anne Hecksteden ◽  
Christopher Weyh ◽  
Kristina Gebhardt ◽  
...  

The purpose of this study was to investigate blood-based biomarkers and their regulation with regard to different recovery-stress states. A total of 35 male elite athletes (13 badminton, 22 soccer players) were recruited, and two venous blood samples were taken: one in a ‘recovered’ state (REC) after a minimum of one-day rest from exercise and another one in a ‘non-recovered’ state (NOR) after a habitual loading microcycle. Overall, 23 blood-based biomarkers of different physiologic domains, which address inflammation, muscle damage, and tissue repair, were analyzed by Luminex assays. Across all athletes, only creatine kinase (CK), interleukin (IL-) 6, and IL-17A showed higher concentrations at NOR compared to REC time points. In badminton players, higher levels of CK and IL-17A at NOR were found. In contrast, a higher value for S100 calcium-binding protein A8 (S100A8) at REC was found in badminton players. Similar differences were found for BDNF in soccer players. Soccer players also showed increased levels of CK, and IL-6 at NOR compared to REC state. Several molecular markers were shown to be responsive to differing recovery-stress states, but their suitability as biomarkers in training must be further validated.


2019 ◽  
Vol 8 (9) ◽  
pp. 1320
Author(s):  
Kazumasa Oda ◽  
Hideshi Okada ◽  
Akio Suzuki ◽  
Hiroyuki Tomita ◽  
Ryo Kobayashi ◽  
...  

Endothelial disorders are related to various diseases. An initial endothelial injury is characterized by endothelial glycocalyx injury. We aimed to evaluate endothelial glycocalyx injury by measuring serum syndecan-1 concentrations in patients during comprehensive medical examinations. A single-center, prospective, observational study was conducted at Asahi University Hospital. The participants enrolled in this study were 1313 patients who underwent comprehensive medical examinations at Asahi University Hospital from January 2018 to June 2018. One patient undergoing hemodialysis was excluded from the study. At enrollment, blood samples were obtained, and study personnel collected demographic and clinical data. No treatments or exposures were conducted except for standard medical examinations and blood sample collection. Laboratory data were obtained by the collection of blood samples at the time of study enrolment. According to nonlinear regression, the concentrations of serum syndecan-1 were significantly related to age (p = 0.016), aspartic aminotransferase concentration (AST, p = 0.020), blood urea nitrogen concentration (BUN, p = 0.013), triglyceride concentration (p < 0.001), and hematocrit (p = 0.006). These relationships were independent associations. Endothelial glycocalyx injury, which is reflected by serum syndecan-1 concentrations, is related to age, hematocrit, AST concentration, BUN concentration, and triglyceride concentration.


HPB Surgery ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Robert Kleinert ◽  
Roger Wahba ◽  
Christoph Bangard ◽  
Klaus Prenzel ◽  
Arnulf H. Hölscher ◽  
...  

Background. Radiofrequency (RF-) assisted liver resection devices like the Habib sealer induce a necrotic resection plane from which a small margin of necrotic liver tissue remains in situ. The aim of the present paper was to report our long-time experience with the new resection method and the morphological characteristics of the remaining necrotic resection plane. Methods. 64 RF-assisted liver resections were performed using the Habib sealer. Followup was assessed at defined time points. Results. The postoperative mortality was 3,6% and morbidity was 18%. The followup revealed that the necrotic zone was detectable in all analyzed CT and MRI images as a hypodense structure without any contrast enhancement at all time points, irrespectively of the time interval between resection and examination. Conclusion. Liver resection utilizing radiofrequency-induced resection plane coagulation is a safe alternative to the established resection techniques. The residual zone of coagulation necrosis remains basically unchanged during a followup of three years. This has to be kept in mind when evaluating the follow up imaging of these patients.


Author(s):  
Anne-Sophie Schuurman ◽  
Anirudh Tomer ◽  
K. Martijn Akkerhuis ◽  
Ewout J. Hoorn ◽  
Jasper J. Brugts ◽  
...  

Abstract Background High mortality and rehospitalization rates demonstrate that improving risk assessment in heart failure patients remains challenging. Individual temporal evolution of kidney biomarkers is associated with poor clinical outcome in these patients and hence may carry the potential to move towards a personalized screening approach. Methods In 263 chronic heart failure patients included in the prospective Bio-SHiFT cohort study, glomerular and tubular biomarker measurements were serially obtained according to a pre-scheduled, fixed trimonthly scheme. The primary endpoint (PE) comprised cardiac death, cardiac transplantation, left ventricular assist device implantation or heart failure hospitalization. Personalized scheduling of glomerular and tubular biomarker measurements was compared to fixed scheduling in individual patients by means of a simulation study, based on clinical characteristics of the Bio-SHiFT study. For this purpose, repeated biomarker measurements and the PE were jointly modeled. For personalized scheduling, using this fitted joint model, we determined the optimal time point of the next measurement based on the patient’s individual risk profile as estimated by the joint model and the maximum information gain on the patient’s prognosis. We compared the schedule’s capability of enabling timely intervention before the occurrence of the PE and number of measurements needed. Results As compared to a pre-defined trimonthly scheduling approach, personalized scheduling of glomerular and tubular biomarker measurements showed similar performance with regard to prognostication, but required a median of 0.4–2.7 fewer measurements per year. Conclusion Personalized scheduling is expected to reduce the number of patient visits and healthcare costs. Thus, it may contribute to efficient monitoring of chronic heart failure patients and could provide novel opportunities for timely adaptation of treatment. Graphic abstract


Author(s):  
V.A. Logvin ◽  
◽  
S.A. Sheptunov ◽  

The conditions for the hardening of tools in accordance with the author’s technological routes in the optimal time interval are considered using the functional dependence of the serviceability of plasma generators. This dependence takes into account the workability of the technical devices involved in processing the laying batch of tools in the speci ed time interval. The probability of performing the production process in the estimated time is represented by the product of the trouble-free operation of each glow discharge plasma generator involved in the nishing processing of tools that require a different type of plasma exposure in a certain sequence and duration.


Sign in / Sign up

Export Citation Format

Share Document