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Comparative evaluation of the effects of atorvastatin and lovastatin on the pharmacokinetics of aliskiren in rats

The worldwide increase in the number patients with high blood pressure poses serious clinical challenges. Little is known regarding the interactions between the various drugs used to treat heart diseases. The present study evaluates and compares the effects of administration of multiple doses of...

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Main Authors: Sharaf, Amal, El-Shazly, Kamal A., Abd El Latif, Amera, Abdelkawy, Khaled S., Elbarbry, Fawzy, Khalifa, Hazim O.
Format: Article
Language:English
Published: Penerbit Universiti Kebangsaan Malaysia 2021
Online Access:http://journalarticle.ukm.my/16921/1/23.pdf
http://journalarticle.ukm.my/16921/
https://www.ukm.my/jsm/malay_journals/jilid50bil3_2021/KandunganJilid50Bil3_2021.html
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spelling my-ukm.journal.169212021-06-28T15:45:21Z http://journalarticle.ukm.my/16921/ Comparative evaluation of the effects of atorvastatin and lovastatin on the pharmacokinetics of aliskiren in rats Sharaf, Amal El-Shazly, Kamal A. Abd El Latif, Amera Abdelkawy, Khaled S. Elbarbry, Fawzy Khalifa, Hazim O. The worldwide increase in the number patients with high blood pressure poses serious clinical challenges. Little is known regarding the interactions between the various drugs used to treat heart diseases. The present study evaluates and compares the effects of administration of multiple doses of atorvastatin or lovastatin on the pharmacokinetics of aliskiren in rats in an effort to determine their underlying mechanisms. A total of 90 healthy female albino rats were randomly divided into three groups. All groups were treated with aliskiren by oral gavage at 8.57 mg/kg daily for 14 days. In addition to aliskiren, group 2 received atorvastatin at a dose of 1.143 mg/kg for 7 days. In addition to aliskiren, group 3 received lovastatin at a dose of 1.143 mg/kg for 7 days. After blood samples were collected at specific time intervals, aliskiren concentrations were determined using liquid chromatography-tandem mass spectrometry. Relative to the control treatment, atorvastatin treatment resulted in non-significant alterations in the pharmacokinetic parameters of aliskiren. In contrast, lovastatin resulted in a significant increase in the area under the curve, peak plasma concentration, and elimination half-life by 21, 10, and 72%, respectively. Additionally, lovastatin significantly reduced oral clearance by 23%. Inhibition of aliskiren metabolism via the hepatic CYP3A subfamily and/or inhibition of intestinal P-glycoprotein and/or the CYP3A subfamily was identified as a possible mechanism. This study is the first to report that only lovastatin causes a marked increase in aliskiren bioavailability. Caution should be taken when lovastatin and aliskiren are administrated concomitantly in clinical practice. Penerbit Universiti Kebangsaan Malaysia 2021-03 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/16921/1/23.pdf Sharaf, Amal and El-Shazly, Kamal A. and Abd El Latif, Amera and Abdelkawy, Khaled S. and Elbarbry, Fawzy and Khalifa, Hazim O. (2021) Comparative evaluation of the effects of atorvastatin and lovastatin on the pharmacokinetics of aliskiren in rats. Sains Malaysiana, 50 (3). pp. 829-837. ISSN 0126-6039 https://www.ukm.my/jsm/malay_journals/jilid50bil3_2021/KandunganJilid50Bil3_2021.html
institution Universiti Kebangsaan Malaysia
building Tun Sri Lanang Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Kebangsaan Malaysia
content_source UKM Journal Article Repository
url_provider http://journalarticle.ukm.my/
language English
description The worldwide increase in the number patients with high blood pressure poses serious clinical challenges. Little is known regarding the interactions between the various drugs used to treat heart diseases. The present study evaluates and compares the effects of administration of multiple doses of atorvastatin or lovastatin on the pharmacokinetics of aliskiren in rats in an effort to determine their underlying mechanisms. A total of 90 healthy female albino rats were randomly divided into three groups. All groups were treated with aliskiren by oral gavage at 8.57 mg/kg daily for 14 days. In addition to aliskiren, group 2 received atorvastatin at a dose of 1.143 mg/kg for 7 days. In addition to aliskiren, group 3 received lovastatin at a dose of 1.143 mg/kg for 7 days. After blood samples were collected at specific time intervals, aliskiren concentrations were determined using liquid chromatography-tandem mass spectrometry. Relative to the control treatment, atorvastatin treatment resulted in non-significant alterations in the pharmacokinetic parameters of aliskiren. In contrast, lovastatin resulted in a significant increase in the area under the curve, peak plasma concentration, and elimination half-life by 21, 10, and 72%, respectively. Additionally, lovastatin significantly reduced oral clearance by 23%. Inhibition of aliskiren metabolism via the hepatic CYP3A subfamily and/or inhibition of intestinal P-glycoprotein and/or the CYP3A subfamily was identified as a possible mechanism. This study is the first to report that only lovastatin causes a marked increase in aliskiren bioavailability. Caution should be taken when lovastatin and aliskiren are administrated concomitantly in clinical practice.
format Article
author Sharaf, Amal
El-Shazly, Kamal A.
Abd El Latif, Amera
Abdelkawy, Khaled S.
Elbarbry, Fawzy
Khalifa, Hazim O.
spellingShingle Sharaf, Amal
El-Shazly, Kamal A.
Abd El Latif, Amera
Abdelkawy, Khaled S.
Elbarbry, Fawzy
Khalifa, Hazim O.
Comparative evaluation of the effects of atorvastatin and lovastatin on the pharmacokinetics of aliskiren in rats
author_facet Sharaf, Amal
El-Shazly, Kamal A.
Abd El Latif, Amera
Abdelkawy, Khaled S.
Elbarbry, Fawzy
Khalifa, Hazim O.
author_sort Sharaf, Amal
title Comparative evaluation of the effects of atorvastatin and lovastatin on the pharmacokinetics of aliskiren in rats
title_short Comparative evaluation of the effects of atorvastatin and lovastatin on the pharmacokinetics of aliskiren in rats
title_full Comparative evaluation of the effects of atorvastatin and lovastatin on the pharmacokinetics of aliskiren in rats
title_fullStr Comparative evaluation of the effects of atorvastatin and lovastatin on the pharmacokinetics of aliskiren in rats
title_full_unstemmed Comparative evaluation of the effects of atorvastatin and lovastatin on the pharmacokinetics of aliskiren in rats
title_sort comparative evaluation of the effects of atorvastatin and lovastatin on the pharmacokinetics of aliskiren in rats
publisher Penerbit Universiti Kebangsaan Malaysia
publishDate 2021
url http://journalarticle.ukm.my/16921/1/23.pdf
http://journalarticle.ukm.my/16921/
https://www.ukm.my/jsm/malay_journals/jilid50bil3_2021/KandunganJilid50Bil3_2021.html
_version_ 1703961609225895936
score 13.226497

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