Pharmacokinetics, pharmacodynamics, safety and tolerability of dabigatran etexilate oral liquid formulation in infants with venous thromboembolism
<p>Venous thromboembolism (VTE) is more frequent in infants than in older children. Treatment guidelines in children are adapted from adult VTE data, but do not currently include direct oral anticoagulant use. Dabigatran etexilate (DE) use in the paediatric population with VTE therefore requir...
Gespeichert in:
| Hauptverfasser: | , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
2017
|
| In: |
Thrombosis and haemostasis
Year: 2017, Jahrgang: 117, Heft: 11, Pages: 2168-2175 |
| ISSN: | 2567-689X |
| DOI: | 10.1160/TH17-06-0429 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1160/TH17-06-0429 Verlag, Volltext: http://www.thieme-connect.de.ezproxy.medma.uni-heidelberg.de/DOI/DOI?10.1160/TH17-06-0429 
|
| Verfasserangaben: | Jacqueline M. L. Halton, Anne-Caroline Picard, Ruth Harper, Fenglei Huang, Martina Brueckmann, Savion Gropper, Hugo Maas, Igor Tartakovsky, Ildar Nurmeev, Lesley G. Mitchell, Leonardo R. Brandão, Elizabeth Chalmers, Manuela Albisetti |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1576715426 | ||
| 003 | DE-627 | ||
| 005 | 20220814171205.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 180621s2017 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1160/TH17-06-0429 |2 doi | |
| 035 | |a (DE-627)1576715426 | ||
| 035 | |a (DE-576)506715426 | ||
| 035 | |a (DE-599)BSZ506715426 | ||
| 035 | |a (OCoLC)1341012054 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Halton, Jacqueline |e VerfasserIn |0 (DE-588)1160045070 |0 (DE-627)1023140748 |0 (DE-576)505462125 |4 aut | |
| 245 | 1 | 0 | |a Pharmacokinetics, pharmacodynamics, safety and tolerability of dabigatran etexilate oral liquid formulation in infants with venous thromboembolism |c Jacqueline M. L. Halton, Anne-Caroline Picard, Ruth Harper, Fenglei Huang, Martina Brueckmann, Savion Gropper, Hugo Maas, Igor Tartakovsky, Ildar Nurmeev, Lesley G. Mitchell, Leonardo R. Brandão, Elizabeth Chalmers, Manuela Albisetti |
| 264 | 1 | |c 2017 | |
| 300 | |a 8 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Publikationsdatum: 30. November 2017 (online) | ||
| 500 | |a Gesehen am 21.06.2018 | ||
| 520 | |a <p>Venous thromboembolism (VTE) is more frequent in infants than in older children. Treatment guidelines in children are adapted from adult VTE data, but do not currently include direct oral anticoagulant use. Dabigatran etexilate (DE) use in the paediatric population with VTE therefore requires verification. We investigated the pharmacokinetic/pharmacodynamic (PK/PD) relationship, safety and tolerability of DE oral liquid formulation (OLF) in infants with VTE (aged < 12 months) who had completed standard anticoagulant treatment in an open-label, phase IIa study. Patients received a single-dose of DE OLF (based on an age- and weight-adjusted nomogram) yielding an exposure comparable to 150 mg in adults. The PK end point was plasma concentration of total dabigatran; PD end points included activated partial thromboplastin time (aPTT), ecarin clotting time (ECT) and diluted thrombin time (dTT). Safety end points included incidence of all bleeding and other adverse events (AEs). Ten patients were screened; eight entered the study (age range, 41-169 days). The geometric mean (gMean) total dabigatran plasma concentrations 2 hours post-dose (around peak concentrations) were 120 ng/mL with a geometric coefficient of variation (gCV) of 62.1%. The gMean at 12 hours post-dosing was 60.4 ng/mL (gCV 30%). PK/PD relationship was linear for ECT and dTT (<i>R</i> <sup>2</sup> = 0.858 and 0.920, respectively), while total dabigatran concentration and aPTT showed a non-linear correlation. There were no deaths, treatment discontinuations or treatment-related AEs. In conclusion, DE was well tolerated without any treatment-related AEs in infants. The observed PK/PD relationships were comparable with the established profile in older patients with VTE.</p> | ||
| 700 | 1 | |a Brückmann, Martina |d 1970- |e VerfasserIn |0 (DE-588)121145069 |0 (DE-627)705257290 |0 (DE-576)292557736 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Thrombosis and haemostasis |d Stuttgart : Thieme, 1976 |g 117(2017), 11, Seite 2168-2175 |h Online-Ressource |w (DE-627)302723188 |w (DE-600)1492370-1 |w (DE-576)079877362 |x 2567-689X |7 nnas |a Pharmacokinetics, pharmacodynamics, safety and tolerability of dabigatran etexilate oral liquid formulation in infants with venous thromboembolism |
| 773 | 1 | 8 | |g volume:117 |g year:2017 |g number:11 |g pages:2168-2175 |g extent:8 |a Pharmacokinetics, pharmacodynamics, safety and tolerability of dabigatran etexilate oral liquid formulation in infants with venous thromboembolism |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1160/TH17-06-0429 |x Verlag |x Resolving-System |3 Volltext |
| 856 | 4 | 0 | |u http://www.thieme-connect.de.ezproxy.medma.uni-heidelberg.de/DOI/DOI?10.1160/TH17-06-0429 |x Verlag |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20180621 | ||
| 993 | |a Article | ||
| 994 | |a 2017 | ||
| 998 | |g 121145069 |a Brückmann, Martina |m 121145069:Brückmann, Martina |d 60000 |e 60000PB121145069 |k 0/60000/ |p 5 | ||
| 999 | |a KXP-PPN1576715426 |e 3013296747 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"type":{"bibl":"article-journal","media":"Online-Ressource"},"title":[{"title_sort":"Pharmacokinetics, pharmacodynamics, safety and tolerability of dabigatran etexilate oral liquid formulation in infants with venous thromboembolism","title":"Pharmacokinetics, pharmacodynamics, safety and tolerability of dabigatran etexilate oral liquid formulation in infants with venous thromboembolism"}],"person":[{"family":"Halton","display":"Halton, Jacqueline","roleDisplay":"VerfasserIn","given":"Jacqueline","role":"aut"},{"display":"Brückmann, Martina","family":"Brückmann","roleDisplay":"VerfasserIn","given":"Martina","role":"aut"}],"note":["Publikationsdatum: 30. November 2017 (online)","Gesehen am 21.06.2018"],"recId":"1576715426","physDesc":[{"extent":"8 S."}],"language":["eng"],"id":{"eki":["1576715426"],"doi":["10.1160/TH17-06-0429"]},"relHost":[{"origin":[{"publisher":"Thieme ; Schattauer","dateIssuedDisp":"1976-","dateIssuedKey":"1976","publisherPlace":"Stuttgart ; Stuttgart"}],"recId":"302723188","disp":"Pharmacokinetics, pharmacodynamics, safety and tolerability of dabigatran etexilate oral liquid formulation in infants with venous thromboembolismThrombosis and haemostasis","pubHistory":["35.1976 -"],"language":["eng"],"id":{"doi":["10.1055/s-00035024"],"zdb":["1492370-1"],"issn":["2567-689X"],"eki":["302723188"]},"physDesc":[{"extent":"Online-Ressource"}],"type":{"bibl":"periodical","media":"Online-Ressource"},"note":["Gesehen am 15.06.2018"],"part":{"extent":"8","issue":"11","text":"117(2017), 11, Seite 2168-2175","year":"2017","pages":"2168-2175","volume":"117"},"title":[{"subtitle":"journal of the International Society on Thrombosis and Haemostasis","title":"Thrombosis and haemostasis","title_sort":"Thrombosis and haemostasis"}]}],"name":{"displayForm":["Jacqueline M. L. Halton, Anne-Caroline Picard, Ruth Harper, Fenglei Huang, Martina Brueckmann, Savion Gropper, Hugo Maas, Igor Tartakovsky, Ildar Nurmeev, Lesley G. Mitchell, Leonardo R. Brandão, Elizabeth Chalmers, Manuela Albisetti"]},"origin":[{"dateIssuedDisp":"2017","dateIssuedKey":"2017"}]} | ||
| SRT | |a HALTONJACQPHARMACOKI2017 | ||