scholarly journals Nonclinical study and applicability of the absorbed dose conversion method with a single biodistribution measurement for targeted alpha-nuclide therapy

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Tetsuya Sakashita ◽  
Shojiro Matsumoto ◽  
Shigeki Watanabe ◽  
Hirofumi Hanaoka ◽  
Yasuhiro Ohshima ◽  
...  
Keyword(s):  
Half Life ◽  
Radioactive Decay ◽  
Absorbed Dose ◽  
Compartment Model ◽  
Optimal Timing ◽  
Post Injection ◽  
Single Measurement ◽  
New Formalism ◽  
Conversion Method ◽  
Nuclide Therapy

Abstract Background We recently reported a new absorbed dose conversion method, RAP (RAtio of Pharmacokinetics), for 211At-meta-astatobenzylguanidine (211At-MABG) using a single biodistribution measurement, the percent injected dose/g. However, there were some mathematical ambiguities in determining the optimal timing of a single measurement of the percent injected dose/g. Thus, we aimed to mathematically reconstruct the RAP method and to examine the optimal timing of a single measurement. Methods We derived a new formalism of the RAP dose conversion method at time t. In addition, we acquired a formula to determine the optimal timing of a single measurement of the percent injected dose/g, assuming the one-compartment model for biological clearance. Results We investigated the new formalism’s performance using a representative RAP coefficient with radioactive decay weighting. Dose conversions by representative RAP coefficients predicted the true [211At]MABG absorbed doses with an error of 10% or less. The inverses of the representative RAP coefficients plotted at 4 h post-injection, which was the optimal timing reported in the previous work, were very close to the new inverses of the RAP coefficients 4 h post-injection. Next, the behavior of the optimal timing was analyzed by radiolabeled compounds with physical half-lives of 7.2 h and 10 d on various biological clearance half-lives. Behavior maps of optimal timing showed a tendency to converge to a constant value as the biological clearance half-life of a target increased. The areas of optimal timing for both compounds within a 5% or 10% prediction error were distributed around the optimal timing when the biological clearance half-life of a target was equal to that of the reference. Finally, an example of RAP dose conversion was demonstrated for [211At]MABG. Conclusions The RAP dose conversion method renovated by the new formalism was able to estimate the [211At]MABG absorbed dose using a similar pharmacokinetics, such as [131I]MIBG. The present formalism revealed optimizing imaging time points on absorbed dose conversion between two radiopharmaceuticals. Further analysis and clinical data will be needed to elucidate the validity of a behavior map of the optimal timing of a single measurement for targeted alpha-nuclide therapy.

scholarly journals Nonclinical Study and Applicability of the Absorbed Dose Conversion Method With a Single Biodistribution Measurement for Targeted Alpha-Nuclide Therapy

2021 ◽  
Author(s):  
Tetsuya Sakashita ◽  
Shojiro Matsumoto ◽  
Shigeki Watanabe ◽  
Hirofumi Hanaoka ◽  
Yasuhiro Ohshima ◽  
...  
Keyword(s):  
Half Life ◽  
Radioactive Decay ◽  
Absorbed Dose ◽  
Compartment Model ◽  
Optimal Timing ◽  
Post Injection ◽  
Single Measurement ◽  
New Formalism ◽  
Conversion Method ◽  
Nuclide Therapy

Abstract BackgroundWe recently reported a new absorbed dose conversion method, RAP (RAtio of Pharmacokinetics), for 211At-meta-astatobenzylguanidine (211At-MABG) using a single biodistribution measurement (%ID/g). However, there were some mathematical ambiguities in determing the optimal timing of a single measurement of %ID/g. Thus, we aimed to mathematically reconstruct the RAP method and to examine the optimal timing of a single measurement. ResultsWe derived a new formalism of the RAP dose conversion method at time t and investigated the new formalism’s performance using a representative RAP coefficient with radioactive-decay weighting. Dose conversions by representative RAP coefficients predicted the true [211At]MABG absorbed doses with an error of 10% or less. The inverses of the representative RAP coefficients plotted at 4 h post-injection, which was the optimal timing reported in the previous work, were very close to the new inverses of the RAP coefficients 4 h post-injection. Next, we acquired a formula to determine the optimal timing of a single measurement of %ID/g, assuming the one-compartment model for biological clearance. The behavior of the optimal timing was analyzed by radiolabeled compounds with physical half-lives of 7.2 h and 10 d on various biological clearance half-lives. Behavior maps of optimal timing showed a tendency to converge to a constant value as the biological clearance half-life of a target increased. The areas of optimal timing for both compounds within a 5% or 10% prediction error were distributed around the optimal timing when the biological clearance half-life of a target was equal to that of the reference. Finally, an example of RAP dose conversion was demonstrated for [211At]MABG.ConclusionsThe RAP dose conversion method renovated by the new formalism was able to estimate the [211At]MABG absorbed dose using a similar pharmacokinetics, such as [131I]MIBG. The present formalism revealed optimizing imaging time points on absorbed dose conversion between two radiopharmaceuticals. Further analysis and clinical data will be needed to elucidate the validity of a behavior map of the optimal timing of a single measurement for targeted alpha-nuclide therapy.

scholarly journals Advancement of pharmacokinetic models of iohexol in patients aged 70 years or older with impaired kidney function

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Max Taubert ◽  
Elke Schaeffner ◽  
Peter Martus ◽  
Markus van der Giet ◽  
Uwe Fuhr ◽  
...  
Keyword(s):  
Random Effects ◽  
Compartment Model ◽  
Optimal Timing ◽  
Population Pharmacokinetic ◽  
Optimal Sampling ◽  
Post Injection ◽  
Concentration Data ◽  
Compartment Models ◽  
Three Compartment Model ◽  
The Impact

AbstractPlasma clearance of iohexol is a pivotal metric to quantify glomerular filtration rate (GFR), but the optimal timing and frequency of plasma sampling remain to be assessed. In this study, we evaluated the impact of a Bayesian estimation procedure on iohexol clearance estimates, and we identified an optimal sampling strategy based on data in individuals aged 70+. Assuming a varying number of random effects, we re-estimated previously developed population pharmacokinetic two- and three-compartment models in a model development group comprising 546 patients with iohexol concentration data up to 300 min post injection. Model performance and optimal sampling times were assessed in an evaluation group comprising 104 patients with reduced GFR and concentration data up to 1440 min post injection. Two- and three-compartment models with random effects for all parameters overestimated clearance values (bias 5.07 and 4.40 mL/min, respectively) and underpredicted 24-h concentrations (bias − 14.5 and − 12.0 µg/ml, respectively). Clearance estimates improved distinctly when limiting random effects of the three-compartment model to clearance and central volume of distribution. Two blood samples, one early and one 300 min post injection, were sufficient to estimate iohexol clearance. A simplified three-compartment model is optimal to estimate iohexol clearance in elderly patients with reduced GFR.

Withdrawal of cefoperazone with milk after intramammary administration in dairy cows – prospective and retrospective analysis

2017 ◽  
Vol 20 (2) ◽  
pp. 261-268
Author(s):  
A. Burmańczuk ◽  
T. Grabowski ◽  
T. Błądek ◽  
C. Kowalski ◽  
P. Dębiak
Keyword(s):  
Dairy Cows ◽  
Half Life ◽  
Drug Distribution ◽  
Compartment Model ◽  
Clinical Mastitis ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Lactation Period ◽  
Milk Samples ◽  
Drug Concentrations

Abstract The aim of the study was to carry out retrospective and prospective comparative analyses of the pharmacokinetics of CEF after single intramammary (IMM) administration in cows. The prospective study (study A) was conducted on 9 dairy cows of the Polish Black-White race with clinical mastitis during the lactation period. Milk samples were collected at 2, 4, 6, 8, 10, 24, 36, 48, 72 and 84 h after single IMM administration of 250 mg of CEF to one quarter. Drug concentrations in milk samples were determined by HPLC-MS/MS technique and the results of the pharmacokinetic analysis were compared to those obtained in previous studies based on the microbiological (study B) and HPLC-UV methods (study C and D). Pharmacokinetic parameters were calculated based on adapted two-compartment model of drug distribution. One of the findings of the comparison of the analysed investigations is that the CEF kinetics determined with the microbiological method is consistent with the results obtained by the authors of this paper. Both studies yielded similar results of the key pharmacokinetic parameters related to the level of the drug distribution to tissues and elimination half-life. In the pharmacodynamic analysis, the observations in all four studies were entirely consistent and have shown lower values of T>MIC90 in healthy animals and significantly higher values in infected dairy cows. The comparison of studies A, B, C, and D revealed that the time of complete CEF wash-out of 90.90% varied and amounted to 5.7, 8.0, 2.2, and 2.2 days after administration of the drug, respectively. It was confirmed that not only the type of the analytical method but also correct sampling have a significant impact on determination of the correct value of the drug half-life after IMM administration. The comparative analysis of studies in which the milk yield was high and low allows a conclusion that this parameter in the case of CEF has no significant effect on T>MIC90.

Pharmacokinetics and Tissue Residues of Sulfathiazole and Sulfamethazine in Pigs

1994 ◽  
Vol 57 (9) ◽  
pp. 796-801 ◽  
Author(s):  
LIEVE S. G. VAN POUCKE ◽  
CARLOS H. VAN PETEGHEM
Keyword(s):  
Intravenous Injection ◽  
Half Life ◽  
Intramuscular Injection ◽  
Compartment Model ◽  
Absolute Bioavailability ◽  
Pharmacokinetic Parameters ◽  
Tissue Concentrations ◽  
Single Intravenous Injection ◽  
The Individual ◽  
Residue Study

The plasma pharmacokinetics and tissue penetration of sulfathiazole (ST) and sulfamethazine (SM) after intravenous and intramuscular injection in pigs were studied. Following a single intravenous dose of 40 mg ST/kg of bodyweight or 80 mg SM/kg of bodyweight, the plasma ST and SM concentrations were best fitted to a two-compartment model. The areas under the curve were 447 ± 39 and 1485 ± 41 mg/h/L, clearances were 0.090 ± 0.007 and 0.054 ± 0.001 L/kg/h, volumes of distribution were 1.16 ± 0.16 and 0.77 ± 0.06 L/kg, half-lifes in distribution phase were l.18 ± 0.57 and 0.23 ± 0.16 h and half-lifes in eliminations phase were 9.0 ± l.6 and 9.8 ± 0.6 h. When the two compounds were administered simultaneously as a single intravenous injection, the pharmacokinetic parameters for ST were not significantly different. The values for SM show statistical differences for some important parameters: α, β and the AUC0–>∞ were significantly decreased and t1/2α, Vd and CIB were significantly increased. It can be concluded that after a single intravenous injection of 40 mg/kg, sulfathiazole has a high tl/2β resulting in higher tissue concentrations. This half-life, which is higher than what is reported in the literature, is not influenced by the simultaneous presence of sulfamethazine. The tl/2β for sulfamethazine after a single intravenous injection of 80 mg/kg is comparable to the data from the literature and is not influenced by the presence of sulfathiazole. Sulfathiazole and SM were also administered simultaneously as an intramuscular injection to healthy pigs at a dosage of 40 and 80 mg/kg bodyweight. Pharmacokinetic experiments were conducted on three pigs. From this pharmacokinetic study it can be concluded that upon a single intramuscular administration of 40 mg/kg of ST and 80 mg/kg of SM the absolute bioavailability in pigs is 0.92 ± 0.04 for ST and l.01 ± 0.07 for SM. Six pigs received five intramuscular im) injections as a single dose of ST and SM every 24 h for five consecutive days for the residue study. The pigs were slaughtered at different times after the last dose was given and samples were taken from various tissues and organs. Concentrations were determined by a microbiological method and a HPTLC method. No edible tissue contained more than 100 μg/kg of the individual sulfonamides after 10 days of withdrawal. It means that adult animals which have a shorter half-life and thus lower tissue concentrations will certainly meet the economic community EC) maximum residue limits after a 10 days withdrawal period.

scholarly journals Application of the radionuclide 210Pb in glaciology – an overview

2020 ◽  
Vol 66 (257) ◽  
pp. 447-456 ◽  
Author(s):  
Heinz W. Gäggeler ◽  
Leonhard Tobler ◽  
Margit Schwikowski ◽  
Theo M. Jenk
Keyword(s):  
Half Life ◽  
Arid Regions ◽  
Noble Gas ◽  
Radioactive Decay ◽  
Ice Cores ◽  
Snow Accumulation ◽  
The Earth ◽  
Special Cases ◽  
Glacier Flow

Abstract210Pb is an environmental radionuclide with a half-life of 22.3 years, formed in the atmosphere via radioactive decay of radon (222Rn). 222Rn itself is a noble gas with a half-life of 3.8 days and is formed via radioactive decay of uranium (238U) contained in the Earth crust from where it constantly emanates into the atmosphere. 210Pb atoms attach to aerosol particles, which are then deposited on glaciers via scavenging with fresh snow. Due to its half-life, ice cores can be dated with this radionuclide over roughly one century, depending on the initial 210Pb activity concentration. Optimum 210Pb dating is achieved for cold glaciers with no – or little – influence by percolating meltwater. This paper presents an overview which not only includes dating of cold glaciers but also some special cases of 210Pb applications in glaciology addressing temperate glaciers, glaciers with negative mass balance, sublimation processes on glaciers in arid regions, determination of annual net snow accumulation as well as glacier flow rates.

scholarly journals Real Life Population Pharmacokinetics Modelling of Eight Factors VIII in Patients with Severe Haemophilia A: Is It Always Relevant to Switch to an Extended Half-Life?

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 380 ◽  
Author(s):  
Quentin Allard ◽  
Zoubir Djerada ◽  
Claire Pouplard ◽  
Yohann Repessé ◽  
Dominique Desprez ◽  
...  
Keyword(s):  
Half Life ◽  
Random Effect ◽  
Real Life ◽  
Compartment Model ◽  
Central Compartment ◽  
Peripheral Compartment ◽  
Population Pharmacokinetic ◽  
Severe Haemophilia ◽  
Fviii Activity ◽  
Data Files

We retrospectively analysed the data files of 171 adults and 87 children/adolescents with severe haemophilia, except for 14 patients (moderate; minor) (1), to develop a global population pharmacokinetic (PK) model for eight factors VIII (FVIII) that could estimate individual PK parameters for targeting the desired level of FVIII activity (FVIII:C); and (2) to compare half-life (HL) in patients switching from a standard half-life (SHL) to an extended half-life (EHL) and evaluate the relevance of the switch. One-stage clotting assay for the measurement of FVIII activity (FVIII:C, IU/mL) was used for population PK modelling. The software, Monolix version 2019R1, was used for non-linear mixed-effects modelling. A linear two-compartment model best described FVIII:C. The estimated PK parameters (between-subject variability) were: 2640 mL (23.2%) for volume of central compartment (V1), 339 mL (46.8%) for volume of peripheral compartment (V2), 135 mL/h for Q (fixed random effect), and 204 mL/h (34.9%) for clearance (Cl). Weight, age, and categorical covariate EHL were found to influence Cl and only weight for V1. This model can be used for all of the FVIII cited in the study. Moreover, we demonstrated, in accordance with previous studies, that Elocta had longer half-life (EHL) than SHL (mean ratio: 1.48) as compared to Advate, Factane, Kogenate, Novoeight, and Refacto.

Pharmacokinetic Considerations of Misonidazole in Therapeutics

1984 ◽  
Vol 3 (1) ◽  
pp. 29-36 ◽  
Author(s):  
I. Matheson ◽  
P.N. Plowman ◽  
A. Johnston
Keyword(s):  
Half Life ◽  
Peak Concentration ◽  
Optimal Timing ◽  
High Dose ◽  
Marked Variation ◽  
Time To Peak ◽  
Conventional Dose ◽  
Frequent Sampling

The pharmacokinetics of misonidazole have been studied in 6 patients with special emphasis on determination of the peak concentration in plasma and saliva. Frequent sampling was performed over 4 h and a marked variation in absorption half-life (range 4 - 125 min) and time to peak range (0.5 - 6.5 h) was found. The optimal timing of irradiation is discussed. In addition to a conventional dose, one of the patients received high dose misonidazole; the pharmacokinetics are compared.

scholarly journals Radon content in Danish till deposits: relationship with redox conditions and age

1969 ◽  
Vol 20 ◽  
pp. 39-42
Author(s):  
Peter Gravesen ◽  
Peter Roll Jakobsen
Keyword(s):  
Water Content ◽  
Clay Minerals ◽  
Organic Material ◽  
Half Life ◽  
Radioactive Decay ◽  
Decay Chain ◽  
Redox Conditions ◽  
Transport Rate ◽  
Radon Content

Radon (222Rn) is a radioactive, noble insoluble gas with a half-life of 3.8 days. It belongs to the uranium (238U) decay chain where radon is formed from radium (226Ra). Uranium and radium are built into mineral structures or are, for example, adsorbed on the surface of clay minerals, limonite or organic material. When radon is formed by radioactive decay from radium, parts of it enter the pores of rocks and soils and are transported by diffusive or advective forces in the pores. The transport rate depends on the permeability and water content in the pores (Nazaroff 1992).

scholarly journals Where does it go? The fate of thiocyanate in the aquarium water and blood plasma of Amphiprion clarkii after exposure to cyanide

2020 ◽  
Author(s):  
J. Alexander Bonanno ◽  
Nancy E. Breen ◽  
Michael F. Tlusty ◽  
Lawrence J. Andrade ◽  
Andrew L. Rhyne
Keyword(s):  
Blood Plasma ◽  
Plasma Levels ◽  
Half Life ◽  
Compartment Model ◽  
Direct Exposure ◽  
Coral Reef Ecosystems ◽  
Aquarium Water ◽  
Acquity Uplc ◽  
Species Specific ◽  
Amphiprion Clarkii

ABSTRACTThe illegal practice of cyanide fishing continues to damage coral reef ecosystems throughout the Indo-Pacific. To combat this destructive fishing method, a simple, reliable test to detect whether or not a fish has been captured using cyanide (CN) is needed. This study analyzed the toxicokinetics of acute, pulsed CN exposure as well as chronic exposure to thiocyanate (SCN), the major metabolite of CN, in the clownfish species, Amphiprion clarkii. Fish were pulse exposed to 50 ppm CN for 20 or 45 seconds or chronically exposed to 100 ppm SCN for 12 days. Blood plasma levels of SCN were measured following derivatization to SCN-bimane using an Acquity UPLC I-Class and Q-Exactive hybrid Quadrupole-Orbitrap HRAM mass spectrometer or directly by HPLC-UV. After exposure to CN, depending on the duration of exposure, SCN plasma levels reached a maximum concentration (300–470 ppb) 0.13–0.17 days after exposure, had a 0.1 to 1.2 day half-life, and often did not return to baseline levels. The half-life of plasma SCN after direct exposure to SCN was found to be 0.13 days, similar to the CN exposure, and that SCN in the holding water would often drop below detection. Finally, we observed that when a fish, never exposed to SCN, was placed in aquarium water spiked with SCN, there was a steady decrease in aqueous SCN concentration over 24 hours until it could no longer be detected. This pattern was repeated with a second sequential dose. These results demonstrate that A. clarkii do not excrete SCN after CN exposure, but in fact can absorb low concentrations of SCN from water, refuting several publications. It appears that A. clarkii exhibit a classic two compartment model where SCN is rapidly eliminated from the blood plasma and is distributed throughout the tissue but not excreted in their urine. This study demonstrates that SCN may be used as a marker of CN exposure only if fish are tested shortly after exposure. There is species specific variability in response to CN, and studies of other taxa need to be performed before this test can be deployed in the field.

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