scholarly journals A simple linear model for the simulation of plasma concentration-time curves based on the two-compartment open model.

1984 ◽  
Vol 32 (3) ◽  
pp. 1096-1105
Author(s):  
EIJI MIZUTA
Keyword(s):  
Plasma Concentration ◽  
Linear Model ◽  
Open Model ◽  
Simple Linear Model ◽  
Concentration Time ◽  
Compartment Open Model

scholarly journals Physiologically Based Pharmacokinetic Models of Probenecid and Furosemide to Predict Transporter Mediated Drug-Drug Interactions

2020 ◽  
Vol 37 (12) ◽  
Author(s):  
Hannah Britz ◽  
Nina Hanke ◽  
Mitchell E. Taub ◽  
Ting Wang ◽  
Bhagwat Prasad ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Organic Anion ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Time Profiles ◽  
Pbpk Models ◽  
Physiologically Based Pharmacokinetic ◽  
Concentration Time ◽  
Anion Transporter ◽  
Physiologically Based

Abstract Purpose To provide whole-body physiologically based pharmacokinetic (PBPK) models of the potent clinical organic anion transporter (OAT) inhibitor probenecid and the clinical OAT victim drug furosemide for their application in transporter-based drug-drug interaction (DDI) modeling. Methods PBPK models of probenecid and furosemide were developed in PK-Sim®. Drug-dependent parameters and plasma concentration-time profiles following intravenous and oral probenecid and furosemide administration were gathered from literature and used for model development. For model evaluation, plasma concentration-time profiles, areas under the plasma concentration–time curve (AUC) and peak plasma concentrations (Cmax) were predicted and compared to observed data. In addition, the models were applied to predict the outcome of clinical DDI studies. Results The developed models accurately describe the reported plasma concentrations of 27 clinical probenecid studies and of 42 studies using furosemide. Furthermore, application of these models to predict the probenecid-furosemide and probenecid-rifampicin DDIs demonstrates their good performance, with 6/7 of the predicted DDI AUC ratios and 4/5 of the predicted DDI Cmax ratios within 1.25-fold of the observed values, and all predicted DDI AUC and Cmax ratios within 2.0-fold. Conclusions Whole-body PBPK models of probenecid and furosemide were built and evaluated, providing useful tools to support the investigation of transporter mediated DDIs.

scholarly journals A model system for investigating the biliary excretion of an anion in the rat

1975 ◽  
Vol 148 (2) ◽  
pp. 303-307 ◽  
Author(s):  
G M Powell ◽  
J G Jones ◽  
A H Olavesen ◽  
C G Curtis
Keyword(s):  
Kinetic Analysis ◽  
Continuous Infusion ◽  
Biliary Excretion ◽  
Essential Feature ◽  
Model System ◽  
Open Model ◽  
Compartment Open Model

1. The biliary excretion of phenolphthalein di[35S]sulphate was studied in rats. 2. The conjugate was administered by continuous infusion at rates of 3, 4.5, 6, 9 and 12 mug/min, and kinetic analysis of the rate of biliary excretion was consistent with a two-compartment open-model system. 3. The results obtained after single injections of the ester were also consistent with the model. 4. An essential feature of the model is the presence of a compartment into which the ester may pass as an alternative to direct excretion via the bile. 5. It is suggested that such a compartment may be located within the liver.

Simultaneous determination of 1,3-dicaffeoylquinic acid and caffeic acid in rat plasma by liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study

2015 ◽  
Vol 7 (8) ◽  
pp. 3587-3592 ◽  
Author(s):  
Guoliang Dai ◽  
Shitang Ma ◽  
Bingting Sun ◽  
Tao Gong ◽  
Shijia Liu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Plasma Concentration ◽  
Rat Plasma ◽  
Tandem Mass ◽  
Concentration Time ◽  
Chromatography Tandem Mass Spectrometry ◽  
Dicaffeoylquinic Acid ◽  
Liquid Chromatography Tandem Mass

The figure shows the average plasma concentration–time curves after an intravenous administration of 4 mL kg−1 Dengzhanxixin injection to rats.

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.

Predictability of plasma concentration–time curves in humans using single-species allometric scaling of chimeric mice with humanized liver

Xenobiotica ◽  
2015 ◽  
Vol 45 (7) ◽  
pp. 605-614 ◽  
Author(s):  
Seigo Sanoh ◽  
Yoichi Naritomi ◽  
Mami Fujimoto ◽  
Koya Sato ◽  
Akio Kawamura ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Allometric Scaling ◽  
Single Species ◽  
Chimeric Mice ◽  
Concentration Time

scholarly journals Variable Absorption of Clavulanic Acid After an Oral Dose of 25 mg/kg of Clavubactin® and Synulox® in Healthy Cats

2002 ◽  
Vol 2 ◽  
pp. 1369-1378 ◽  
Author(s):  
Tom B. Vree ◽  
Eric Dammers ◽  
Eri van Duuren
Keyword(s):  
Single Dose ◽  
Plasma Concentration ◽  
Oral Dose ◽  
Clavulanic Acid ◽  
Phase I Study ◽  
Pharmacokinetic Parameters ◽  
High Efficacy ◽  
Dose Ratio ◽  
Concentration Time ◽  
Crossover Phase

The aims of this investigation were to calculate the pharmacokinetic parameters and to identify parameters, based on individual plasma concentration-time curves of amoxicillin and clavulanic acid in cats, that may govern the observed differences in absorption of both drugs. The evaluation was based on the data from plasma concentration-time curves obtained following a single-dose, open, randomised, two-way crossover phase-I study, each involving 24 female cats treated with two Amoxi-Clav formulations (formulation A was Clavubactin® and formulation was B Synulox® ; 80/20 mg, 24 animals, 48 drug administrations). Plasma amoxicillin and clavulanic acid concentrations were determined using validated bioassay methods. The half-life of elimination of amoxicillin is 1.2 h (t1/2= 1.24 ± 0.28 h, Cmax= 12.8 ± 2.12 μg/ml), and that of clavulanic acid 0.6 h (t1/2= 0.63 ± 0.16 h, Cmax= 4.60 ± 1.68 μg/ml). There is a ninefold variation in the AUCtof clavulanic acid for both formulations, while the AUCtof amoxicillin varies by a factor of two. The highest clavulanic acid AUCtvalues indicate the best absorption; all other data indicate less absorption. Taking into account that the amoxicillin–to–clavulanic acid dose ratio in the two products tested was 4:1, the blood concentration ratios may actually vary much more, apparently without compromising the products’ high efficacy against susceptible microorganisms.

Safety, Tolerability and Pharmacokinetics of BIBN 4096 BS, the First Selective Small Molecule Calcitonin Gene-Related Peptide Receptor Antagonist, Following Single Intravenous Administration in Healthy Volunteers

Cephalalgia ◽  
2004 ◽  
Vol 24 (8) ◽  
pp. 645-656 ◽  
Author(s):  
M Iovino ◽  
U Feifel ◽  
C-L Yong ◽  
J-M Wolters ◽  
G Wallenstein
Keyword(s):  
Plasma Concentration ◽  
Receptor Antagonist ◽  
Small Molecule ◽  
Intravenous Administration ◽  
Calcitonin Gene Related Peptide ◽  
Related Peptide ◽  
Concentration Time ◽  
Calcitonin Gene ◽  
Dose Levels ◽  
Single Intravenous Administration

BIBN 4096 BS ([R-(R∗,S∗)]-N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl] pentyl]amino]-1-[(3,5-dibromo-4-hydroxyphenyl)methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-,1-piperidinecarboxamide) is the first selective, highly potent, small molecule, nonpeptide calcitonin gene-related peptide (CGRP) receptor antagonist, which has been developed for the treatment of acute migraine. The objective of this study was to obtain information on the safety, tolerability and pharmacokinetics of BIBN 4096 BS following single intravenous administration of rising doses (0.1, 0.25, 0.5, 1, 2.5, 5 and 10 mg) in 55 healthy male and female volunteers. The study was of single-centre, double-blind (within dose levels), placebo-controlled, randomized, single rising dose design. Blood pressure, pulse rate, respiratory rate, ECG, laboratory tests and forearm blood flow did not reveal any clinically relevant, drug-induced changes. Sixteen adverse events (AEs) were reported by eight of 41 volunteers after BIBN 4096 BS compared to five AEs reported by four of 14 volunteers after placebo. Approximately two-thirds of all AEs related to active treatment occurred at the highest dose of 10 mg. At this dose level, all AEs were confined to the three BIBN 4096 BS-treated females, and consisted mainly of transient and mild paresthesias. Paresthesias were the single most frequent AE, whereas fatigue was the AE which occurred in the highest number of subjects. Only two AEs were of moderate intensity, all remaining AEs were of mild intensity. No serious AEs were reported. The local tolerability after intravenous administration was good. In summary, intravenously administered BIBN 4096 BS revealed a very favourable safety profile over the dose range tested in both genders. Generally well tolerated at all dose levels, it was of satisfactory tolerability in female subjects at the highest dose of 10 mg. The plasma concentration-time courses of BIBN 4096 BS showed multicompartmental disposition characteristics. Mean maximum concentration (Cmax) values appeared to be dose-proportional. Based on the results from the two high dose levels (5 and 10 mg) with sufficient individual subject data, BIBN 4096 BS exhibited a total plasma clearance (CL) of approximately 12 l/h and an apparent volume of distribution at steady state (Vss) of approximately 20 l, resulting in a terminal half-life (t1/2) of approximately 2.5 h. Inter-individual variability was moderate with a coefficient of variation of approximately 45% based on the area under the plasma concentration-time curve (AUC) values. The mean renal clearance (CLR) was approximately 2 l/h, suggesting that renal excretion plays only a minor role in the elimination of unchanged BIBN 4096 BS.

Sign in / Sign up

Export Citation Format

Share Document