67Gallium Kinetics in the Blood of Patients with Malignant Tumors

1983 ◽  
Vol 22 (03) ◽  
pp. 155-158
Author(s):  
M. K. Maiga ◽  
P. Koeppe ◽  
F. Keller
Keyword(s):  
Kinetic Parameters ◽  
Malignant Tumors ◽  
Clinical Investigation ◽  
Compartment Model ◽  
Bimodal Distribution ◽  
Volume Of Distribution ◽  
Least Square ◽  
Peripheral Compartment ◽  
Limited Information ◽  
Tumor Patients

67GaIlium was injected into 60 patients with malignant tumors and into 42 patients in whom malignant tumors had been excluded by clinical investigation. 67Ga kinetics in blood were evaluated by non-linear least square regression computer analysis according to an open 2-compartment model where elimination proceeds from the peripheral compartment. Parameters of 67Ga kinetics in tumor patients showed a bimodal distribution, as was also the case in patients without tumors. No difference could be demonstrated between kinetic parameters of tumor patients and patients without tumors. In 4 patients, 67Ga kinetics could be evaluated before and after treatment of their malignant tumors, but a decrease in the volume of distribution was the single alteration of kinetic parameters occurring after treatment. This decrease may be explained by a smaller peripheral compartment resulting from the loss of tumor mass after treatment. Nevertheless, we conclude that the evaluation of 67Ga kinetics in blood will provide only limited information about the presence, size and growth rate of malignant tumors in man.

scholarly journals The pharmacokinetics of [18F]UCB-H revisited in the healthy non-human primate brain

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sébastien Goutal ◽  
Martine Guillermier ◽  
Guillaume Becker ◽  
Mylène Gaudin ◽  
Yann Bramoullé ◽  
...  
Keyword(s):  
Slow Component ◽  
Specific Binding ◽  
Compartment Model ◽  
Brain Regions ◽  
Volume Of Distribution ◽  
Pharmacokinetic Data ◽  
Limited Information ◽  
Positron Emission ◽  
Human Primate

Abstract Background Positron Emission Tomography (PET) imaging of the Synaptic Vesicle glycoprotein (SV) 2A is a new tool to quantify synaptic density. [18F]UCB-H was one of the first promising SV2A-ligands to be labelled and used in vivo in rodent and human, while limited information on its pharmacokinetic properties is available in the non-human primate. Here, we evaluate the reliability of the three most commonly used modelling approaches for [18F]UCB-H in the non-human cynomolgus primate, adding the coupled fit of the non-displaceable distribution volume (VND) as an alternative approach to improve unstable fit. The results are discussed in the light of the current state of SV2A PET ligands. Results [18F]UCB-H pharmacokinetic data was optimally fitted with a two-compartment model (2TCM), although the model did not always converge (large total volume of distribution (VT) or large uncertainty of the estimate). 2TCM with coupled fit K1/k2 across brain regions stabilized the quantification, and confirmed a lower specific signal of [18F]UCB-H compared to the newest SV2A-ligands. However, the measures of VND and the influx parameter (K1) are similar to what has been reported for other SV2A ligands. These data were reinforced by displacement studies using [19F]UCB-H, demonstrating only 50% displacement of the total [18F]UCB-H signal at maximal occupancy of SV2A. As previously demonstrated in clinical studies, the graphical method of Logan provided a more robust estimate of VT with only a small bias compared to 2TCM. Conclusions Modeling issues with a 2TCM due to a slow component have previously been reported for other SV2A ligands with low specific binding, or after blocking of specific binding. As all SV2A ligands share chemical structural similarities, we hypothesize that this slow binding component is common for all SV2A ligands, but only hampers quantification when specific binding is low.

Kinetics of dodecanedioic acid triglyceride in rats

1999 ◽  
Vol 276 (3) ◽  
pp. E497-E502
Author(s):  
A. de Gaetano ◽  
G. Mingrone ◽  
M. Castagneto ◽  
G. Benedetti ◽  
A. V. Greco ◽  
...  
Keyword(s):  
High Performance ◽  
Compartment Model ◽  
High Performance Liquid Chromatographic ◽  
Volume Of Distribution ◽  
Peripheral Compartment ◽  
Parameter Estimates ◽  
Tissue Uptake ◽  
Male Wistar Rats ◽  
Dodecanedioic Acid ◽  
Kinetics Of

The kinetics of the triglyceride of dodecanedioic acid (TGDA) has been investigated in 30 male Wistar rats after a rapid intravenous bolus injection. TGDA and its product of hydrolysis, nonesterified dodecanedioic acid (NEDA), were measured in plasma samples taken at different times using an improved high-performance liquid chromatographic method. The 24-h urinary excretion of TGDA was 1.54 ± 0.37 μmol, corresponding to ∼0.67% of the administered amount. Several kinetics models were considered, including central and peripheral compartments for the triglyceride and the free forms and expressing transports between compartments with combinations of linear, carrier-limited, or time-varying mechanisms. The parameter estimates of the kinetics of TGDA and of NEDA were finally obtained using a three-compartment model in which the transfer of TGDA to NEDA was assumed to be linear, through a peripheral compartment, and the tissue uptake of NEDA was assumed to be carrier limited. TGDA had a large volume of distribution (∼0.5 l/kg body wt) with a fast disappearance rate from plasma (0.42 min−1), whereas NEDA had a very small volume of distribution (∼0.04 l/kg body wt) and a tissue uptake with maximal transport rate of 0.636 mM/min. In conclusion, this first study on the triglyceride form of dodecanedioic acid indicates that it is rapidly hydrolyzed and that both triglyceride and nonesterified forms are excreted in the urine to a very low extent. The tissue uptake rate of NEDA is consistent with the possibility of achieving substantial energy delivery, should it be added to parenteral nutrition formulations. Furthermore, the amount of sodium administered with the triglyceride form is one-half of that necessary with the free diacid.

scholarly journals The Pharmacokinetics of [18F]UCB-H Revisited in The Healthy Non-Human Primate Brain

2020 ◽  
Author(s):  
Sébastien Goutal ◽  
Martine Guillermier ◽  
Guillaume Becker ◽  
Mylène Gaudin ◽  
Yann Bramoullé ◽  
...  
Keyword(s):  
Slow Component ◽  
Specific Binding ◽  
Compartment Model ◽  
Brain Regions ◽  
Volume Of Distribution ◽  
Binding Potential ◽  
Pharmacokinetic Data ◽  
Limited Information ◽  
Human Primate

Abstract Background Positron Emission Tomography (PET) imaging of the Synaptic Vesicle glycoprotein (SV) 2A is a new tool to quantify synaptic density. [18F]UCB-H was one of the first promising SV2A-ligands to be labelled and used in vivo in rodent and human, while limited information on its pharmacokinetic properties is available in the non-human primate. Here, we aimed to characterize [18F]UCB-H in the non-human cynomolgus primate and to discuss the obtained results in the light of the current state of SV2A PET ligands.Results [18F]UCB-H pharmacokinetic data was optimally fitted with a two-compartment model (2TCM), even though a slow component led to instability for the estimation of k3 and k4, and hence the total volume of distribution. 2TCM with coupled fit K1/k2 across brain regions stabilized the quantification, and confirmed a lower non-displaceable binding potential, BPND (estimated by k3/k4), of [18F]UCB-H compared to the newest SV2A-ligands. However, the non-displaceable distribution volume (VND) and the influx parameter (K1) is similar to what has been reported for other SV2A ligands. These data were reinforced by displacement studies using [19F]UCB-H, demonstrating only 50 % displacement of the total [18F]UCB-H signal at maximal occupancy of SV2A. Conclusions Modeling issues with a 2TCM due to a slow component have previously been reported for other SV2A ligands with low specific binding, or after blocking of specific binding. As all SV2A ligands share chemical structural similarities, we hypothesize that this slow binding component is common for all SV2A ligands, but only hampers quantification when specific binding is low.

scholarly journals Pharmacokinetic Profile of Kaurenoic Acid after Oral Administration of Araliae Continentalis Radix Extract Powder to Humans

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 253
Author(s):  
Eun-Jeong Choi ◽  
Go-Wun Choi ◽  
Seung-Jeong Yang ◽  
Yong-Bok Lee ◽  
Hea-Young Cho
Keyword(s):  
Plasma Concentrations ◽  
Compartment Model ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Efflux Transporters ◽  
Peripheral Compartment ◽  
Simple Liquid ◽  
Usual Dose ◽  
Kaurenoic Acid

The objective of this study was to characterize pharmacokinetics (PKs) of kaurenoic acid (KAU) after administration of the clinical usual dose of Araliae Continentalis Radix extract powder to Korean subjects for the first time and evaluate the mechanism of its absorption in vitro. A simple, sensitive, and selective analytical method was developed for the detection of KAU in human plasma. Concentrations of KAU were quantified by ultra-performance liquid chromatography tandem mass spectrometry after simple liquid–liquid extraction. This pharmacokinetic model of KAU was best described by a two-compartment model with first-order absorption. To identify efflux transporters involved in the absorption of KAU, a Caco-2 monolayer model was used. Estimated PK parameters were: systemic clearance, 23.89 L/h; inter-compartmental clearance, 15.55 L/h; rate constant for absorption, 1.72 h−1; volume of distribution of the central compartment, 24.44 L; and volume of distribution of the peripheral compartment, 64.05 L. Results from Caco-2 bidirectional transport study suggested that KAU was a potential substrate of efflux transporters. In summary, PKs of KAU were successfully characterized after administration of a usual dose of Araliae continentalis Radix extract powder in human with the newly developed bioanalytical method and the mechanism of absorption of KAU was identified clearly.

scholarly journals P72 Maturation of sildenafil clearance in prematurely born infants with BPD associated pulmonary hypertension

2019 ◽  
Vol 104 (6) ◽  
pp. e47.1-e47
Author(s):  
H Nikrawesh ◽  
AGJ Engbers ◽  
S Völler ◽  
SHP Simons ◽  
BCP Koch ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Limited Information ◽  
Mixed Effect ◽  
Time Profiles ◽  
Nonlinear Mixed Effect ◽  
Postmenstrual Age ◽  
Oral Doses ◽  
Prematurely Born Infants

BackgroundSildenafil is used as an off-label treatment for bronchopulmonary dysplasia (BPD) associated pulmonary hypertension in prematurely born infants. As there is only limited information on the pharmacokinetics (PK) of sildenafil in this population, the aim of this study is to investigate the PK of sildenafil in prematurely born infants with BPD associated pulmonary hypertension.MethodIn this multicentre study, a population PK model for sildenafil in prematurely born infants was developed based on samples obtained using opportunistic sampling during clinical use of sildenafil. Data of seven subjects (42 plasma samples) were analysed by nonlinear mixed-effect modelling (NONMEM®7.3). Median (range) gestational age (GA) was 26.1 (24.1–27.6) weeks, current bodyweight 1960 (632–3157) grams, birthweight 635 (465–1125) grams and postnatal age (PNA) at start of therapy 64.9 (10.9–89) days. The median (range) treatment duration was 4.9 (1.6–13.1) weeks, with six subjects receiving oral doses of median 2.6 mg/kg/day (1.5–5.3) in three doses and one subject receiving oral and intravenous doses of 6.7 mg/kg/day in two doses.ResultsThe plasma concentration time profiles of sildenafil were best described by a one compartment model. Clearance (CL) and volume of distribution (Vd) for a child with a PNA of 64.9 days and bodyweight of 1.96 kg was 4.42 L/h ((RSE) 11%) and 29.5 L (32%), respectively. PNA was found to significantly influence CL, resulting in an increase of 10.7% in a week, and 43% in a month for a 65-day old infant. No other covariates (i.e. bodyweight, birthweight, GA, postmenstrual age and sex) were identified for CL or Vd.ConclusionIn this PK study, we characterised the pharmacokinetics of sildenafil in prematurely born infants and found that clearance increases with PNA. Due to the limited sample size in this study, further research in a larger population is needed to extend these findings.Disclosure(s)Nothing to disclose

scholarly journals Pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis

2016 ◽  
pp. AAC.01657-16 ◽  
Author(s):  
Danny Tsai ◽  
Penelope Stewart ◽  
Rajendra Goud ◽  
Stephen Gourley ◽  
Saliya Hewagama ◽  
...  
Keyword(s):  
Severe Sepsis ◽  
Critically Ill ◽  
Total Body Weight ◽  
Compartment Model ◽  
Central Compartment ◽  
Volume Of Distribution ◽  
Peripheral Compartment ◽  
Population Pharmacokinetic ◽  
Pharmacokinetic Data ◽  
Population Pharmacokinetic Study

Objectives: There are no available pharmacokinetic data to guide piperacillin dosing in critically ill Australian Indigenous patients despite numerous reported physiological differences. This study aimed to describe the population pharmacokinetics of piperacillin in critically ill Australian Indigenous patients with severe sepsis.Methods: A population pharmacokinetic study of Indigenous patients with severe sepsis was conducted in a remote hospital intensive care unit. Plasma samples were collected over two dosing intervals and assayed by validated chromatography. Population pharmacokinetic modelling was conducted using Pmetrics®.Results: Nine patients were recruited and a two compartment model adequately described the data. Piperacillin clearance (CL), volume of distribution of the central compartment (Vc), distribution rate constant from central to peripheral compartment and from peripheral to central compartment were 5.6 ± 3.2 L/h, 14.5 ± 6.6 L, 1.5 ± 0.4 h-1and 1.8 ± 0.9 h-1respectively, where CL and Vcwere found to be described by creatinine clearance (CrCL) and total body weight respectively.Conclusion: In this patient population, piperacillin demonstrated high interindividual pharmacokinetic variability. CrCL were found to be the most important determinant of piperacillin pharmacokinetics.

scholarly journals Variability in Estimated Modelled Insulin Secretion

2021 ◽  
pp. 193229682199112
Author(s):  
Jennifer J. Ormsbee ◽  
Hannah J. Burden ◽  
Jennifer L. Knopp ◽  
J. Geoffrey Chase ◽  
Rinki Murphy ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Kinetic Parameters ◽  
Pancreatic Beta Cells ◽  
Compartment Model ◽  
Interquartile Range ◽  
Cumulative Distribution ◽  
Model Framework ◽  
Intravenous Glucose ◽  
C Peptide ◽  
Model Based

Background: The ability to measure insulin secretion from pancreatic beta cells and monitor glucose-insulin physiology is vital to current health needs. C-peptide has been used successfully as a surrogate for plasma insulin concentration. Quantifying the expected variability of modelled insulin secretion will improve confidence in model estimates. Methods: Forty-three healthy adult males of Māori or Pacific peoples ancestry living in New Zealand participated in an frequently sampled, intravenous glucose tolerance test (FS-IVGTT) with an average age of 29 years and a BMI of 33 kg/m2. A 2-compartment model framework and standardized kinetic parameters were used to estimate endogenous pancreatic insulin secretion from plasma C-peptide measurements. Monte Carlo analysis (N = 10 000) was then used to independently vary parameters within ±2 standard deviations of the mean of each variable and the 5th and 95th percentiles determined the bounds of the expected range of insulin secretion. Cumulative distribution functions (CDFs) were calculated for each subject for area under the curve (AUC) total, AUC Phase 1, and AUC Phase 2. Normalizing each AUC by the participant’s median value over all N = 10 000 iterations quantifies the expected model-based variability in AUC. Results: Larger variation is found in subjects with a BMI > 30 kg/m2, where the interquartile range is 34.3% compared to subjects with a BMI ≤ 30 kg/m2 where the interquartile range is 24.7%. Conclusions: Use of C-peptide measurements using a 2-compartment model and standardized kinetic parameters, one can expect ~±15% variation in modelled insulin secretion estimates. The variation should be considered when applying this insulin secretion estimation method to clinical diagnostic thresholds and interpretation of model-based analyses such as insulin sensitivity.

scholarly journals Effect of polyaspartic acid on pharmacokinetics of gentamicin after single intravenous dose in the dog.

1996 ◽  
Vol 40 (5) ◽  
pp. 1237-1241 ◽  
Author(s):  
T Whittem ◽  
K Parton ◽  
K Turner
Keyword(s):  
Aspartic Acid ◽  
Elimination Rate ◽  
Volume Of Distribution ◽  
Intravenous Dose ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Peripheral Compartment ◽  
Single Intravenous Dose ◽  
Polyaspartic Acid ◽  
Peripheral Tissues

The effects of poly-L-aspartic acid on the pharmacokinetics of gentamicin were examined by using a randomized crossover trial design with the dog. When analyzed according to a three-compartment open model, poly-L-aspartic acid reduced some first-order rate equation constants (A3, lambda 1, and lambda 3), the deep peripheral compartment exit microconstant (k31), the elimination rate constant (k(el)), and the area under the concentration-time curve from 0 to 480 h (AUC0-480) (0.21-, 0.60-, 0.26-, 0.27-, 0.72-, and 0.76-fold, respectively; P < 0.05) but increased the volume of distribution at steady state (Vss), the volume of distribution calculated by the area method (V(area)), the apparent volume of the peripheral compartment (Vp), and all mean time parameters. These results suggested that poly-L-aspartic acid increased the distribution of gentamicin to or binding within the deep peripheral compartment and that poly-L-aspartic acid may have delayed gentamicin transit through the peripheral tissues. In contrast, poly-L-aspartic acid did not alter pharmacokinetic parameters relevant to the central or shallow peripheral compartments to a clinically significant extent. Although gentamicin's pharmacokinetic parameters of relevance to therapeutic drug monitoring were not directly altered, this study has provided pharmacokinetic evidence that poly-L-aspartic acid alters the peripheral distribution of gentamicin. This pharmacokinetic interaction occurred after a single intravenous dose of each drug. Therefore, this interaction should be investigated further, before polyaspartic acid can be considered for use as a clinical nephroprotectant.

Ketamine kinetics: decerebrate vs. intact cats

1979 ◽  
Vol 57 (8) ◽  
pp. 878-881 ◽  
Author(s):  
James E. Heavner ◽  
Duane C. Bloedow
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Drug Dose ◽  
The Body ◽  
Pharmacokinetic Parameters ◽  
Peripheral Compartment ◽  
Blood Concentrations ◽  
Open Model ◽  
Apparent Volume Of Distribution ◽  
Compartment Open Model

Pharmacokinetic parameters of a ketamine (10 mg/kg, iv) bolus in decerebrate and intact cats were compared. A two-compartment open model best described the data in both groups. The apparent volume of distribution of the peripheral compartment, the apparent volume of distribution of the drug in the body, and the half-life of the postdistributive phase were significantly less (p < 0.05) in the decerebrate animals. These results emphasize the importance of correlating behavior and neuronal activity with plasma or blood concentrations of drug in animals rather than assuming that, for a given drug dose, blood (and thus tissue) levels of the agent will be similar regardless of how the animal is prepared for study.

Population Pharmacokinetics of Recombinant Factor VIIa in Volunteers Anticoagulated with Acenocoumarol

1998 ◽  
Vol 80 (07) ◽  
pp. 109-113 ◽  
Author(s):  
Patrice Nony ◽  
Elisabeth Erhardtsen ◽  
Sylvie Delair ◽  
Patrick Ffrench ◽  
Marc Dechavanne ◽  
...  
Keyword(s):  
Factor Viia ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Individual Variability ◽  
Factor Vii ◽  
Recombinant Activated Factor Vii ◽  
Activated Factor Vii ◽  
Dose Ranging ◽  
Endogenous Activity ◽  
Dose Dependent

SummaryThis study establishes a population PK model for FVII clotting activity (FVII:C) after injection of recombinant activated factor VII (rFVIIa) to healthy volunteers. Twenty eight volunteers, anticoagulated with acenocoumarol, received one or two rFVIIa injections, with dose ranging from 5 to 320 μg/kg. The FVII:C kinetic was fitted to a 2 compartment model, with continuous “endogenous perfusion” mimicking endogenous activity. Estimated clearance was 2.4 l/h (20% inter-individual variability and 9% inter-period variability). The volume of distribution at steady-state appeared to be significantly dose dependent: 78 ml/kg for doses ≤20 μg/kg and 88 ml/kg for doses >20 μg/kg respectively, with 16% inter-individual variability. The dose producing 50% of the maximum drop of INR was estimated to be 2.2 μg/kg. The model will be used to better define the dosage regimen for future clinical developments.

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