On the Accuracy of a One-Compartment Approach for Determination of Drug Terminal Half-Life

Berezhkovskiy, Leonid M.

doi:10.1002/jps.23565

Cited by 4 publications

(4 citation statements)

References 10 publications

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“…Based on this clearance rate, the mean residence time (MRT) for the peptide is calculated to be 159 min and its terminal volume of distribution (V t ) is 4258 ml•kg -1 . Using Q 0 ’ (the corrected zero-time radioactivity) rather than Q 0 (the uncorrected) in calculating the AUC of plasma radioactivity (1.69•e 8 CPM•ml −1 min −1 ) for the interval of 0–726 min (726 min, the time point when 99% of the injected isotope would have been eliminated at the terminal clearance rate, k t ), the total body clearance (CL) is determined to be 27.1 ml•kg −1 min −1 [Berezhkovskiy 2013].…”

Section: Resultsmentioning

confidence: 99%

“…The corresponding half-lives t1/2(i) , t1/2(i)’ and t1/2(t) for k i , k i ’ and k t , respectively, are calculated (ln2/ k ). The terminal phase is assumed based on the nearsteady clearance kinetics during the late phase (8–20 min, .... ) and is used as a single-compartment model to characterize the clearance kinetics of the peptide [Berezhkovskiy, 2013].…”

Section: Figurementioning

confidence: 99%

“…V t , terminal volume of distribution [Berezhkovskiy, 2013b]. CL, total body clearance = 125 I-dose/AUC Q0-726 (AUC, area under the curve, trapezoid method [Berezhkovskiy, 2013b]. AUC Q0-726 = AUC Q0-20 + AUC Q20-726 , the latter is calculated from Q 20 up to 726 min where 99% of the plasma 125 I-radioactivity is calculated to have been eliminated as predicted from k t .…”

Section: Figurementioning

confidence: 99%

“…AUC Q0-726 = AUC Q0-20 + AUC Q20-726 , the latter is calculated from Q 20 up to 726 min where 99% of the plasma 125 I-radioactivity is calculated to have been eliminated as predicted from k t . MRT, mean residence time [Berezhkovskiy, 2013b].…”

Section: Figurementioning

confidence: 99%

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Clearance kinetics of the VGF-derived neuropeptide TLQP-21

Sahu

Finan

et al. 2018

Neuropeptides

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A small single i.v. dose of [I]TLQP-21 had a terminal half-life of 110 min with a terminal clearance rate constant, k, of 0.0063/min, and an initial half-life of 0.97 min with an initial clearance rate constant, k, of 0.71/min. The total net uptake by adipose tissue accounts for 4.4% of the entire dose equivalent while the liver, pancreas and adrenal gland showed higher uptake. Uptake by the brain was negligible, suggesting that i.v.-injected peptide does not cross the blood-brain-barrier. TLQP-21 sustained isoproterenol-stimulated lipolysis in vivo. Finally, TLQP-21 was rapidly degraded producing several N-terminal and central sequence fragments after 10 and 60 min in plasma in vitro. This study investigated the clearance and stability of TLQP-21 peptide for the first time. While its pro-lipolytic effect supports and extends previous findings, its short half-life and sequential cleavage in the plasma suggest strategies for chemical modifications in order to enhance its stability and therapeutic efficacy.

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Section: Resultsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Clearance kinetics of the VGF-derived neuropeptide TLQP-21

Sahu

Finan

et al. 2018

Neuropeptides

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Time of effect duration and administration interval for sitagliptin in patients with kidney failure

Keller

Hartmann

Czock

2013

Eur J Drug Metab Pharmacokinet

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A measure correlating the time course of the effect with the time course of concentrations could be helpful in drug dosing. We propose a new equation with explicit solutions for calculating the effect duration. A specific effect fraction is selected (fr) and the time of fractional effect duration (TED.fr) can be derived as a function of the elimination half-life by combining linear elimination kinetics with sigmoid effect dynamics. This new measure is applied to the example of sitagliptin, whose elimination half-life increases from 10.1 to 28.4 h in patients with kidney failure. Under normal multiple-dose conditions, the 24-h sitagliptin administration interval corresponds to a 0.90 time of fractional effect duration (TED.90). A dose reduction to one-fourth or 25 mg every 24 h is proposed for patients with kidney failure; this results in a TED.90 of 45 h, i.e. 21 h longer than the proposed 24-h administration interval (+88 %). The proportional dosing alternative of 100 mg every 96 h would result in a TED.90 of 64 h, which is 32 h less than the 96-h administration interval (-33 %). With a half dose of 50 mg and a doubled administration interval of 48 h, the TED.90 is 51 h in kidney failure, only 3 h longer than the latter administration interval (+6 %). We conclude that our general equation can be applied to rapidly calculate the specific time of effect duration for the different dose schedules.

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PepMSND: Integrating Multi-level Feature Engineering and Comprehensive Databases to Enhance in vivo/in vitro Peptide Blood Stability Prediction

Haomeng,

Zhang,

Zhenyu

et al. 2024

Preprint

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Deep learning technology has revolutionized the field of peptides, but key questions such as how to predict the blood stability of peptides remain. While such a task can be accomplished by experiments, it requires much time and cost. Here, to address this challenge, we collect extensive experimental data on peptide stability in blood from public databases and literature and construct a database of peptide blood stability that includes 635 samples. Based on this database, we develop a novel model called PepMSND, integrating KAN, Transformer, GAT and SE(3)-Transformer to make multi-level feature engineering to make peptide stability prediction. Our model can achieve the ACC of 0.8672 and the AUC of 0.9118 on average and outperforms the baseline models. This work can facilitate the development of novel peptides with strong stability, which is crucial for their therapeutic use in clinical applications.

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On the Accuracy of a One-Compartment Approach for Determination of Drug Terminal Half-Life

Cited by 4 publications

References 10 publications

Clearance kinetics of the VGF-derived neuropeptide TLQP-21

Clearance kinetics of the VGF-derived neuropeptide TLQP-21

Time of effect duration and administration interval for sitagliptin in patients with kidney failure

PepMSND: Integrating Multi-level Feature Engineering and Comprehensive Databases to Enhance in vivo/in vitro Peptide Blood Stability Prediction

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