A Comparative Computer Simulation Study of Three Different Sparse-Sampling Methods for the Estimation of Steady-State Area Under the Concentration—time Curve (AUC) and Maximum concentration (Cmax) in Toxicokinetics

1997 ◽  
Vol 86 (5) ◽  
pp. 579-583 ◽  
Author(s):  
Iftekhar Mahmood
Keyword(s):  
Computer Simulation ◽  
Steady State ◽  
Simulation Study ◽  
Maximum Concentration ◽  
Sampling Methods ◽  
Sparse Sampling ◽  
Computer Simulation Study ◽  
Time Curve ◽  
Concentration Time ◽  
State Area

Industrial SBR Process: Computer Simulation Study for Online Estimation of Steady-State Variables Using Neural Networks

2007 ◽  
Vol 1 (3) ◽  
pp. 405-412 ◽  
Author(s):  
Roque J. Minari ◽  
Georgina S. Stegmayer ◽  
Luis M. Gugliotta ◽  
Omar A. Chiotti ◽  
Jorge R. Vega
Keyword(s):  
Neural Networks ◽  
Computer Simulation ◽  
Steady State ◽  
Simulation Study ◽  
State Variables ◽  
Computer Simulation Study ◽  
Online Estimation ◽  
Process Computer

scholarly journals Effects of Food and Omeprazole on a Novel Formulation of Super Bioavailability Itraconazole in Healthy Subjects

2018 ◽  
Vol 62 (12) ◽  
Author(s):  
Julian Lindsay ◽  
Stuart Mudge ◽  
George R. Thompson
Keyword(s):  
Steady State ◽  
Maximum Concentration ◽  
Healthy Adults ◽  
Plasma Exposure ◽  
Open Label ◽  
Time Curve ◽  
Dosing Interval ◽  
Fasted State ◽  
Concentration Time ◽  
Bioavailability Study

ABSTRACT To address the limited bioavailability and intolerance of the conventional itraconazole (ITZ) formulations, a new formulation labeled super bioavailability (SUBA) itraconazole has been developed; however, the specific effects of food and gastric pH are unknown. This study evaluated the pharmacokinetic profile of SUBA itraconazole under fasting and fed conditions, as well as with the concomitant administration of a proton pump inhibitor. First, the effect of food was assessed in an open-label, randomized, crossover bioavailability study of 65-mg SUBA itraconazole capsules (2 65-mg capsules twice a day) in healthy adults (n = 20) under fasting and fed conditions to steady-state levels. Second, an open-label, two-treatment, fixed-sequence comparative bioavailability study in healthy adults (n = 28) under fasted conditions compared the pharmacokinetics of a single oral dose of SUBA itraconazole capsules (2 65-mg capsules/day) with and without coadministration of daily omeprazole delayed-release capsules (1 40-mg capsule/day) under steady-state conditions. In the fed and fasted states, SUBA itraconazole demonstrated similar concentrations at the end of the dosing interval, with modestly lower total and peak ITZ exposure being shown when it was administered under fed conditions than when it was administered in the fasted state, with fed state/fasted state ratios of 78.09% (90% confidence interval [CI], 74.49 to 81.86%) for the area under the concentration-time curve over the dosing interval (14,183.2 versus 18,479.8 ng · h/ml), 73.05% (90% CI, 69.01 to 77.33%) for the maximum concentration at steady state (1,519.1 versus 2,085.2 ng/ml), and 91.53% (90% CI, 86.41 to 96.96%) for the trough concentration (1,071.5 versus 1,218.5 ng/ml) being found. When dosed concomitantly with omeprazole, there was a 22% increase in the total plasma exposure of ITZ, as measured by the area under the concentration-time curve from time zero to infinity (P = 0.0069), and a 31% increase in the peak plasma exposure of ITZ, as measured by the maximum concentration (P = 0.0083).

scholarly journals Pharmacokinetic interaction between itraconazole and rifampin in Yucatan miniature pigs.

1996 ◽  
Vol 40 (9) ◽  
pp. 2043-2046 ◽  
Author(s):  
G Kaltenbach ◽  
D Levêque ◽  
J D Peter ◽  
J Salmon ◽  
H Elkhaili ◽  
...  
Keyword(s):  
Steady State ◽  
Standard Deviation ◽  
Maximum Concentration ◽  
Active Metabolite ◽  
Pharmacokinetic Interaction ◽  
Hepatic Metabolism ◽  
Miniature Pig ◽  
Time Curve ◽  
Miniature Pigs ◽  
Concentration Time

The objective of this study was to examine the effects of rifampin on itraconazole pharmacokinetics, at steady state, in three Yucatan miniature pigs. Daily for 3 weeks, the pigs received 200 mg of itraconazole orally at the beginning of each meal, and for the following 2 weeks they received itraconazole orally combined with intravenous administration of rifampin at 10 mg/kg/day. Coadministration of rifampin resulted in an 18-fold decrease in the maximum concentration of itraconazole in serum, from 113.0 (standard deviation [SD] 17.2) to 6.2 (SD, 3.9) ng/ml and a 22-fold decrease in the area under the concentration-time curve, from 1,652.7 (SD, 297.7) to 75.6 (SD, 30.0) ng.h/ml. The active metabolite of itraconazole, hydroxyitraconazole, was undetectable. This study demonstrates that rifampin affects itraconazole kinetics considerably at steady state in this miniature-pig model, probably by inducing hepatic metabolism of itraconazole.

scholarly journals Effect of Steady-State Faldaprevir on the Pharmacokinetics of Steady-State Methadone and Buprenorphine-Naloxone in Subjects Receiving Stable Addiction Management Therapy

2014 ◽  
Vol 59 (1) ◽  
pp. 498-504 ◽  
Author(s):  
David Joseph ◽  
Michael J. Schobelock ◽  
Robert R. Riesenberg ◽  
Bradley D. Vince ◽  
Lynn R. Webster ◽  
...  
Keyword(s):  
Steady State ◽  
Maximum Dose ◽  
Geometric Mean ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Time Curve ◽  
Once Daily ◽  
Concentration Time ◽  
State Concentration ◽  
State Area

ABSTRACTThe effects of steady-state faldaprevir on the safety, pharmacokinetics, and pharmacodynamics of steady-state methadone and buprenorphine-naloxone were assessed in 34 healthy male and female subjects receiving stable addiction management therapy. Subjects continued receiving a stable oral dose of either methadone (up to a maximum dose of 180 mg per day) or buprenorphine-naloxone (up to a maximum dose of 24 mg-6 mg per day) and also received oral faldaprevir (240 mg) once daily (QD) for 8 days following a 480-mg loading dose. Serial blood samples were taken for pharmacokinetic analysis. The pharmacodynamics of the opioid maintenance regimens were evaluated by the objective and subjective opioid withdrawal scales. Coadministration of faldaprevir with methadone or buprenorphine-naloxone resulted in geometric mean ratios for the steady-state area under the concentration-time curve from 0 to 24 h (AUC0–24,ss), the steady-state maximum concentration of the drug in plasma (Cmax,ss), and the steady-state concentration of the drug in plasma at 24 h (C24,ss) of 0.92 to 1.18 for (R)-methadone, (S)-methadone, buprenorphine, norbuprenorphine, and naloxone, with 90% confidence intervals including, or very close to including, 1.00 (no effect), suggesting a limited overall effect of faldaprevir. Although individual data showed moderate variability in the exposures between subjects and treatments, there was no evidence of symptoms of opiate overdose or withdrawal either during the coadministration of faldaprevir with methadone or buprenorphine-naloxone or after faldaprevir dosing was stopped. Similar faldaprevir exposures were observed in the methadone- and buprenorphine-naloxone-treated subjects. In conclusion, faldaprevir at 240 mg QD can be coadministered with methadone or buprenorphine-naloxone without dose adjustment, although given the relatively narrow therapeutic windows of these agents, monitoring for opiate overdose and withdrawal may still be appropriate. (This study has been registered atClinicalTrials.govunder registration no. NCT01637922.)

scholarly journals Pharmacodynamic Optimization for Treatment of Invasive Candida auris Infection

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Alexander J. Lepak ◽  
Miao Zhao ◽  
Elizabeth L. Berkow ◽  
Shawn R. Lockhart ◽  
David R. Andes
Keyword(s):  
Animal Model ◽  
Steady State ◽  
Invasive Candidiasis ◽  
Maximum Concentration ◽  
Multidrug Resistant ◽  
Total Drug ◽  
Candida Auris ◽  
Time Curve ◽  
Content Type ◽  
Concentration Time

ABSTRACT Candida auris is an emerging multidrug-resistant threat. The pharmacodynamics of three antifungal classes against nine C. auris strains was explored using a murine invasive candidiasis model. The total drug median pharmacodynamic (PD) target associated with net stasis was a fluconazole AUC/MIC (the area under the concentration-time curve over 24 h in the steady state divided by the MIC) of 26, an amphotericin B C max/MIC (maximum concentration of drug in serum divided by the MIC) of 0.9, and a micafungin AUC/MIC of 54. The micafungin PD targets for C. auris were ≥20-fold lower than those of other Candida species in this animal model. Clinically relevant micafungin exposures produced the most killing among the three classes.

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