Pharmacokinetic Modeling to Simulate the Concentration-Time Profiles After Dermal Application of Rivastigmine Patch
Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved..
Rivastigmine is an inhibitor of acetylcholinesterases and butyrylcholinesterases for symptomatic treatment of Alzheimer disease and is available as oral and transdermal patch formulations. A dermal absorption pharmacokinetic (PK) model was developed to simulate the plasma concentration-time profile of rivastigmine to answer questions relative to the efficacy and safety risks after misuse of the patch (e.g., longer application than 24 h, multiple patches applied at the same time, and so forth). The model comprised 2 compartments which was a combination of mechanistic dermal absorption model and a basic 1-compartment model. The initial values for the model were determined based on the physicochemical characteristics of rivastigmine and PK parameters after intravenous administration. The model was fitted to the clinical PK profiles after single application of rivastigmine patch to obtain model parameters. The final model was validated by confirming that the simulated concentration-time curves and PK parameters (Cmax and area under the drug plasma concentration-time curve) conformed to the observed values and then was used to simulate the PK profiles of rivastigmine. This work demonstrated that the mechanistic dermal PK model fitted the clinical data well and was able to simulate the PK profile after patch misuse.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2016 |
|---|---|
| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:105 |
|---|---|
| Enthalten in: |
Journal of pharmaceutical sciences - 105(2016), 7 vom: 23. Juli, Seite 2213-21 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Nozaki, Sachiko [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Absorption |
|---|
| Anmerkungen: |
Date Completed 29.11.2017 Date Revised 04.04.2018 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.xphs.2016.04.011 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM26063039X |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM26063039X | ||
| 003 | DE-627 | ||
| 005 | 20231224193818.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231224s2016 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.xphs.2016.04.011 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0868.xml |
| 035 | |a (DE-627)NLM26063039X | ||
| 035 | |a (NLM)27212635 | ||
| 035 | |a (PII)S0022-3549(16)41382-1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Nozaki, Sachiko |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Pharmacokinetic Modeling to Simulate the Concentration-Time Profiles After Dermal Application of Rivastigmine Patch |
| 264 | 1 | |c 2016 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 29.11.2017 | ||
| 500 | |a Date Revised 04.04.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Rivastigmine is an inhibitor of acetylcholinesterases and butyrylcholinesterases for symptomatic treatment of Alzheimer disease and is available as oral and transdermal patch formulations. A dermal absorption pharmacokinetic (PK) model was developed to simulate the plasma concentration-time profile of rivastigmine to answer questions relative to the efficacy and safety risks after misuse of the patch (e.g., longer application than 24 h, multiple patches applied at the same time, and so forth). The model comprised 2 compartments which was a combination of mechanistic dermal absorption model and a basic 1-compartment model. The initial values for the model were determined based on the physicochemical characteristics of rivastigmine and PK parameters after intravenous administration. The model was fitted to the clinical PK profiles after single application of rivastigmine patch to obtain model parameters. The final model was validated by confirming that the simulated concentration-time curves and PK parameters (Cmax and area under the drug plasma concentration-time curve) conformed to the observed values and then was used to simulate the PK profiles of rivastigmine. This work demonstrated that the mechanistic dermal PK model fitted the clinical data well and was able to simulate the PK profile after patch misuse | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a absorption | |
| 650 | 4 | |a clinical pharmacokinetics | |
| 650 | 4 | |a physiologically based pharmacokinetic modeling | |
| 650 | 4 | |a simulations | |
| 650 | 4 | |a transdermal | |
| 650 | 7 | |a Cholinesterase Inhibitors |2 NLM | |
| 650 | 7 | |a Rivastigmine |2 NLM | |
| 650 | 7 | |a PKI06M3IW0 |2 NLM | |
| 700 | 1 | |a Yamaguchi, Masayuki |e verfasserin |4 aut | |
| 700 | 1 | |a Lefèvre, Gilbert |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of pharmaceutical sciences |d 1961 |g 105(2016), 7 vom: 23. Juli, Seite 2213-21 |w (DE-627)NLM000006394 |x 1520-6017 |7 nnns |
| 773 | 1 | 8 | |g volume:105 |g year:2016 |g number:7 |g day:23 |g month:07 |g pages:2213-21 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.xphs.2016.04.011 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 105 |j 2016 |e 7 |b 23 |c 07 |h 2213-21 | ||