Target-mediated drug disposition pharmacokinetic-pharmacodynamic model of Bosentan and Endothelin-1
Background and ObjectivesBosentan is a competitive antagonist on endothelin receptor A and B (ETA and ETB), displacing the endogenous binding partner endothelin-1 (ET-1) from its binding sites. After administration of escalating single doses of 10-750 mg as an intravenous (i.v.) infusion, bosentan s...
Gespeichert in:
| Hauptverfasser: | , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
11 April 2017
|
| In: |
Clinical pharmacokinetics
Year: 2017, Jahrgang: 56, Heft: 12, Pages: 1499-1511 |
| ISSN: | 1179-1926 |
| DOI: | 10.1007/s40262-017-0534-4 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1007/s40262-017-0534-4 Verlag, Volltext: https://link.springer.com/article/10.1007/s40262-017-0534-4 
|
| Verfasserangaben: | Anke-Katrin Volz, Andreas Krause, Walter Emil Haefeli, Jasper Dingemanse, Thorsten Lehr |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1578036992 | ||
| 003 | DE-627 | ||
| 005 | 20230426230758.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 180730s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1007/s40262-017-0534-4 |2 doi | |
| 035 | |a (DE-627)1578036992 | ||
| 035 | |a (DE-576)508036992 | ||
| 035 | |a (DE-599)BSZ508036992 | ||
| 035 | |a (OCoLC)1341014446 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Volz, Anke-Katrin |e VerfasserIn |0 (DE-588)1163541141 |0 (DE-627)1027865690 |0 (DE-576)508037255 |4 aut | |
| 245 | 1 | 0 | |a Target-mediated drug disposition pharmacokinetic-pharmacodynamic model of Bosentan and Endothelin-1 |c Anke-Katrin Volz, Andreas Krause, Walter Emil Haefeli, Jasper Dingemanse, Thorsten Lehr |
| 264 | 1 | |c 11 April 2017 | |
| 300 | |a 13 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Published online: 11 April 2017 | ||
| 500 | |a Gesehen am 30.07.2018 | ||
| 520 | |a Background and ObjectivesBosentan is a competitive antagonist on endothelin receptor A and B (ETA and ETB), displacing the endogenous binding partner endothelin-1 (ET-1) from its binding sites. After administration of escalating single doses of 10-750 mg as an intravenous (i.v.) infusion, bosentan showed dose-dependent pharmacokinetics (PK). The aim of this analysis was to develop a PK model of bosentan after i.v. administration including competitive antagonism with ET-1 and to analyze its influence on blood pressure and heart rate with a combined pharmacokinetic/pharmacodynamic (PK/PD) model.MethodsPK/PD data from 70 young male Caucasian subjects were analyzed after single i.v. administration of 10, 50, 250, 500, and 750 mg of bosentan. Population analyses, simulations, and evaluation were performed using a non-linear mixed-effects modeling approach.ResultsThe PK of bosentan was best described by a two-compartment, target-mediated drug disposition (TMDD) model. ET-1 plasma and urine profiles were successfully integrated into the bosentan two-compartment, TMDD model encompassing competition for the same receptor. A multiple-peak phenomenon of bosentan plasma concentrations after i.v. administration was best described by a diurnal expression or reappearance of ET receptors on the cell surface. Blood pressure was best described by an E max model; heart rate was modeled as a compensatory effect of changes in blood pressure.ConclusionThe developed competitive PK/PD model of bosentan and ET-1 after i.v. administration provides a first step towards understanding the complex PK properties of bosentan and offers a valuable tool for future PK/PD research. | ||
| 700 | 1 | |a Haefeli, Walter E. |d 1958- |e VerfasserIn |0 (DE-588)124572359 |0 (DE-627)656806141 |0 (DE-576)340514221 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Clinical pharmacokinetics |d Berlin [u.a.] : Springer, 1976 |g 56(2017), 12, Seite 1499-1511 |h Online-Ressource |w (DE-627)327644974 |w (DE-600)2043781-X |w (DE-576)10337339X |x 1179-1926 |7 nnas |a Target-mediated drug disposition pharmacokinetic-pharmacodynamic model of Bosentan and Endothelin-1 |
| 773 | 1 | 8 | |g volume:56 |g year:2017 |g number:12 |g pages:1499-1511 |g extent:13 |a Target-mediated drug disposition pharmacokinetic-pharmacodynamic model of Bosentan and Endothelin-1 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1007/s40262-017-0534-4 |x Verlag |x Resolving-System |3 Volltext |
| 856 | 4 | 0 | |u https://link.springer.com/article/10.1007/s40262-017-0534-4 |x Verlag |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20180730 | ||
| 993 | |a Article | ||
| 994 | |a 2017 | ||
| 998 | |g 124572359 |a Haefeli, Walter E. |m 124572359:Haefeli, Walter E. |d 910000 |d 910100 |e 910000PH124572359 |e 910100PH124572359 |k 0/910000/ |k 1/910000/910100/ |p 3 | ||
| 999 | |a KXP-PPN1578036992 |e 3019698480 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"name":{"displayForm":["Anke-Katrin Volz, Andreas Krause, Walter Emil Haefeli, Jasper Dingemanse, Thorsten Lehr"]},"person":[{"display":"Volz, Anke-Katrin","family":"Volz","given":"Anke-Katrin","roleDisplay":"VerfasserIn","role":"aut"},{"given":"Walter E.","role":"aut","roleDisplay":"VerfasserIn","family":"Haefeli","display":"Haefeli, Walter E."}],"id":{"eki":["1578036992"],"doi":["10.1007/s40262-017-0534-4"]},"title":[{"title_sort":"Target-mediated drug disposition pharmacokinetic-pharmacodynamic model of Bosentan and Endothelin-1","title":"Target-mediated drug disposition pharmacokinetic-pharmacodynamic model of Bosentan and Endothelin-1"}],"origin":[{"dateIssuedKey":"2017","dateIssuedDisp":"11 April 2017"}],"recId":"1578036992","relHost":[{"id":{"zdb":["2043781-X"],"eki":["327644974"],"issn":["1179-1926"]},"pubHistory":["1.1976 -"],"title":[{"title":"Clinical pharmacokinetics","title_sort":"Clinical pharmacokinetics"}],"origin":[{"publisher":"Springer ; Adis Intern.","dateIssuedDisp":"1976-","publisherPlace":"Berlin [u.a.] ; Auckland","dateIssuedKey":"1976"}],"type":{"media":"Online-Ressource","bibl":"periodical"},"part":{"extent":"13","volume":"56","issue":"12","text":"56(2017), 12, Seite 1499-1511","year":"2017","pages":"1499-1511"},"language":["eng"],"note":["Gesehen am 06.03.13","Ungezählte Beil.: Suppl"],"recId":"327644974","physDesc":[{"extent":"Online-Ressource"}],"disp":"Target-mediated drug disposition pharmacokinetic-pharmacodynamic model of Bosentan and Endothelin-1Clinical pharmacokinetics"}],"note":["Published online: 11 April 2017","Gesehen am 30.07.2018"],"type":{"media":"Online-Ressource","bibl":"article-journal"},"physDesc":[{"extent":"13 S."}],"language":["eng"]} | ||
| SRT | |a VOLZANKEKATARGETMEDI1120 | ||