Dose-Dependent Bioavailability and CYP3A Inhibition Contribute to Non-Linear Pharmacokinetics of Voriconazole

2016 ◽  
Vol 55 (12) ◽  
pp. 1535-1545 ◽  
Author(s):  
Nicolas Hohmann ◽  
Franziska Kocheise ◽  
Alexandra Carls ◽  
Jürgen Burhenne ◽  
Johanna Weiss ◽  
...  
Keyword(s):  
Linear Pharmacokinetics ◽  
Non Linear ◽  
Dose Dependent

scholarly journals Novel analysis of drug-drug interactions reveals the appearance of non-linear dose dependence under the single drug treatment

2020 ◽  
Author(s):  
Yh. Taguchi ◽  
Turki Turki
Keyword(s):  
Gene Expression ◽  
Drug Interactions ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Tensor Decomposition ◽  
Dose Dependence ◽  
Linear Dose ◽  
Non Linear ◽  
New Interactions ◽  
Dose Dependent

ABSTRACTThe accurate prediction of new interactions between drugs is important for avoiding unknown (mild or severe) adverse reactions to drug combinations. The development of effective in silico methods for evaluating drug interactions based on gene expression data requires an under-standing of how various drugs alter gene expression. Current computational methods for the prediction of drug-drug interactions (DDIs) utilize data for known DDIs to predict unknown interactions. However, these methods are limited in the absence of known predictive DDIs. To improve DDIs’ interpretation, a recent study has demonstrated strong non-linear (i.e., dose-dependent) effects of DDIs. In this study, we present a new unsupervised learning approach involving tensor decomposition (TD)-based unsupervised feature extraction (FE) in 3D. We utilize our approach to reanalyze available gene expression profiles for Saccharomyces cerevisiae. We found that non-linearity is possible, even for single drugs. Thus, non-linear dose-dependence cannot always be attributed to DDIs. Our analysis provides a basis for the design of effective methods for evaluating DDIs.

scholarly journals Non-linear pharmacokinetics of high-dose intravenous verapamil

1997 ◽  
Vol 44 (3) ◽  
pp. 255-260 ◽  
Author(s):  
G. Toffoli ◽  
I. Robieux ◽  
D. Fantin ◽  
M. Gigante ◽  
S. Frustaci ◽  
...  
Keyword(s):  
High Dose ◽  
Linear Pharmacokinetics ◽  
Non Linear

To Apply Microdosing or Not? Recommendations to Single Out Compounds with Non-Linear Pharmacokinetics

2015 ◽  
Vol 55 (1) ◽  
pp. 1-15 ◽  
Author(s):  
Sieto Bosgra ◽  
Maria L. H. Vlaming ◽  
Wouter H. J. Vaes
Keyword(s):  
Linear Pharmacokinetics ◽  
Non Linear

Non-Linear Pharmacokinetics of Atomoxetine in Adult Japanese Patients With ADHD

2016 ◽  
Vol 24 (3) ◽  
pp. 490-493
Author(s):  
Atsunori Sugimoto ◽  
Yutaro Suzuki ◽  
Naoki Orime ◽  
Taketsugu Hayashi ◽  
Jun Egawa ◽  
...  
Keyword(s):  
High Performance ◽  
Plasma Concentrations ◽  
Japanese Patients ◽  
High Dose ◽  
Linear Pharmacokinetics ◽  
Blood Samples ◽  
Non Linear ◽  
The Difference ◽  
The Relationship ◽  
Atomoxetine Treatment

Objective: The objective was to reveal the relationship between dose and concentration of atomoxetine. Method: Fifty-five blood samples of 33 patients with ADHD were examined using high-performance liquid chromatography. Results: The plasma concentrations were 53.2 ± 67.0, 298.0 ± 390.5, and 639.3 ± 831.9 ng/mL at doses of 40 mg, 80 mg, and 120 mg, and the concentration/dose were 1.33 ± 1.67, 3.73 ± 4.88, and 5.33 ± 6.93 ng/mL/mg, respectively. Statistical analyses revealed a significant correlation between the concentration and the dose of atomoxetine ( p = .004), and a trending toward significance in the difference in the concentration/dose in the three dosage groups ( p = .064). The concentration/dose at 40 and 80 + 120 mg/day were 1.33 ± 1.67 and 4.22 ± 5.53 ng/mL/mg, the latter was significantly higher than the former ( p = .006), which suggested non-linear pharmacokinetics. Conclusion: Clinicians should carefully titrate in high dose atomoxetine treatment.

The non-linear pharmacokinetics of prednisone and prednisolone

1988 ◽  
Vol 9 (4) ◽  
pp. 363-376 ◽  
Author(s):  
James J. Ferry ◽  
John G. Wagner
Keyword(s):  
Linear Pharmacokinetics ◽  
Non Linear
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