Animal model investigation suggests betamethasone alters the pharmacokinetics of amikacin

Corticosteroids, such as betamethasone, are sometimes administered to women who are at risk of pre-term delivery. These corticosteroids cross the placenta to the fetus and decrease respiratory distress syndrome in preterm newborns. Preterm newborns are often susceptible to infections partly due to t...

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Main Authors: Seth Kwabena Amponsah, Kwabena Frimpong-Manso Opuni, Ama Asiedua Donkor
Format: Article
Language:English
Published: International Association of Physical Chemists (IAPC) 2018-12-01
Series:ADMET and DMPK
Subjects:
Online Access:http://pub.iapchem.org/ojs/index.php/admet/article/view/613
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author Seth Kwabena Amponsah
Kwabena Frimpong-Manso Opuni
Ama Asiedua Donkor
author_facet Seth Kwabena Amponsah
Kwabena Frimpong-Manso Opuni
Ama Asiedua Donkor
author_sort Seth Kwabena Amponsah
collection DOAJ
description Corticosteroids, such as betamethasone, are sometimes administered to women who are at risk of pre-term delivery. These corticosteroids cross the placenta to the fetus and decrease respiratory distress syndrome in preterm newborns. Preterm newborns are often susceptible to infections partly due to their immature immune system. Amikacin is one of the aminoglycosides used in the treatment of newborn infections. There is, however, a dearth of information on the effect of prenatal corticosteroids on the disposition of aminoglycosides administered to newborns days later. We evaluated the effect of pre-administration of betamethasone on the disposition of amikacin, 72 h after last dose of betamethasone, using an animal model. The pharmacokinetic parameters of rats administered betamethasone followed by amikacin vis-a-vis rats administered saline followed by amikacin were as follows: Cmax; 16.6 μmol L-1 vs. 31.4 μmol L-1, AUC0→8; 26.8 μmol h L-1 vs. 153.5 μmol h L-1, Ke; 0.26 h-1 vs. 0.18 h-1, and t1/2; 2.6 h vs. 3.9 h, respectively. About a 1.5-fold increase in the elimination of amikacin was observed in the Sprague-Dawley rats pre-treated with betamethasone compared with those pre-treated with saline. This ultimately led to differences in the other pharmacokinetic parameters amongst the two groups of rats. Although an animal model investigation showed some level of interaction, a follow-up study in preterm newborns where possible interaction of the two drugs is studied later than Day 1, is recommended.
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spelling doaj.art-4bdccb67abaf4dbca3ded98bc57e0e212022-12-22T00:12:04ZengInternational Association of Physical Chemists (IAPC)ADMET and DMPK1848-77182018-12-016427928310.5599/admet.613343Animal model investigation suggests betamethasone alters the pharmacokinetics of amikacinSeth Kwabena AmponsahKwabena Frimpong-Manso OpuniAma Asiedua DonkorCorticosteroids, such as betamethasone, are sometimes administered to women who are at risk of pre-term delivery. These corticosteroids cross the placenta to the fetus and decrease respiratory distress syndrome in preterm newborns. Preterm newborns are often susceptible to infections partly due to their immature immune system. Amikacin is one of the aminoglycosides used in the treatment of newborn infections. There is, however, a dearth of information on the effect of prenatal corticosteroids on the disposition of aminoglycosides administered to newborns days later. We evaluated the effect of pre-administration of betamethasone on the disposition of amikacin, 72 h after last dose of betamethasone, using an animal model. The pharmacokinetic parameters of rats administered betamethasone followed by amikacin vis-a-vis rats administered saline followed by amikacin were as follows: Cmax; 16.6 μmol L-1 vs. 31.4 μmol L-1, AUC0→8; 26.8 μmol h L-1 vs. 153.5 μmol h L-1, Ke; 0.26 h-1 vs. 0.18 h-1, and t1/2; 2.6 h vs. 3.9 h, respectively. About a 1.5-fold increase in the elimination of amikacin was observed in the Sprague-Dawley rats pre-treated with betamethasone compared with those pre-treated with saline. This ultimately led to differences in the other pharmacokinetic parameters amongst the two groups of rats. Although an animal model investigation showed some level of interaction, a follow-up study in preterm newborns where possible interaction of the two drugs is studied later than Day 1, is recommended.http://pub.iapchem.org/ojs/index.php/admet/article/view/613ExcretionInteractionPreterm
spellingShingle Seth Kwabena Amponsah
Kwabena Frimpong-Manso Opuni
Ama Asiedua Donkor
Animal model investigation suggests betamethasone alters the pharmacokinetics of amikacin
ADMET and DMPK
Excretion
Interaction
Preterm
title Animal model investigation suggests betamethasone alters the pharmacokinetics of amikacin
title_full Animal model investigation suggests betamethasone alters the pharmacokinetics of amikacin
title_fullStr Animal model investigation suggests betamethasone alters the pharmacokinetics of amikacin
title_full_unstemmed Animal model investigation suggests betamethasone alters the pharmacokinetics of amikacin
title_short Animal model investigation suggests betamethasone alters the pharmacokinetics of amikacin
title_sort animal model investigation suggests betamethasone alters the pharmacokinetics of amikacin
topic Excretion
Interaction
Preterm
url http://pub.iapchem.org/ojs/index.php/admet/article/view/613
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