Pharmacokinetic non-interaction analysis in a fixed-dose formulation in combination of atorvastatin and ezetimibe

Patiño Rodríguez Omar, Torres Roque Irma, Martínez Delgado Maricela, Escobedo Moratilla Abraham, Pérez Urizar José

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

© 2014 Patiño-rodríguez, Torres-roque, Martínez-delgado, Escobedo-moratilla and Pérez-urizar. Recent clinical research has shown that atorvastatin in combination with cholesterol absorption inhibitor ezetimibe significantly reduces LDL-C level in patients with hypercholesterolemia, showing a superior lipid-lowering efficacy compared to statin alone. With no information currently available on the interaction between the two drugs, a pharmacokinetic study was conducted to investigate the influence of ezetimibe on atorvastatin and conversely when the two drugs were coadministered. The purpose of this study was to investigate the presence of differences in the pharmacokinetic profiles of capsules containing atorvastatin 80 mg, ezetimibe 10 mg or the combination of both 80/10 mg administered to healthy Mexican volunteers. This was a randomized, three-period, six-sequences crossover study. 36 eligible subjects aged between 20 to 50 years were included. Blood samples were collected up to 96 h after dosing, and pharmacokinetic parameters were obtained by noncompartmental analysis. Adverse events were evaluated based on subject interviews and physical examinations. Area under the concentration-time curve (AUC) and maximum plasma drug concentration (Cmax) were measured for each drug alone or together and tested for bioequivalencebased hypothesis. The estimation computed (90% confidence intervals) for AUC and Cmax, were 96.04% (85.88%-107.42%) and 97.04% (82.36%-114.35%), respectively for atorvastatin-ezetimibe combination versus atorvastatin alone, while 84.42% (77.19%-92.32%) and 95.60% (82.43%- 110.88%), respectively, for atorvastatin-ezetimibe combination versus ezetimibe alone were estimated. These results suggest that atorvastatin and ezetimibe have no relevant pharmacokinetic drug-drug interaction.
Original languageAmerican English
JournalFrontiers in Pharmacology
DOIs
StatePublished - 1 Jan 2014
Externally publishedYes

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Pharmacokinetics
Pharmaceutical Preparations
Anticholesteremic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Atorvastatin Calcium
Ezetimibe
Hypercholesterolemia
Drug Interactions
Cross-Over Studies
Physical Examination
Capsules
Healthy Volunteers
Confidence Intervals
Interviews
Lipids
Research

Cite this

Omar, Patiño Rodríguez ; Irma, Torres Roque ; Maricela, Martínez Delgado ; Abraham, Escobedo Moratilla ; José, Pérez Urizar. / Pharmacokinetic non-interaction analysis in a fixed-dose formulation in combination of atorvastatin and ezetimibe. In: Frontiers in Pharmacology. 2014.
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abstract = "{\circledC} 2014 Pati{\~n}o-rodr{\'i}guez, Torres-roque, Mart{\'i}nez-delgado, Escobedo-moratilla and P{\'e}rez-urizar. Recent clinical research has shown that atorvastatin in combination with cholesterol absorption inhibitor ezetimibe significantly reduces LDL-C level in patients with hypercholesterolemia, showing a superior lipid-lowering efficacy compared to statin alone. With no information currently available on the interaction between the two drugs, a pharmacokinetic study was conducted to investigate the influence of ezetimibe on atorvastatin and conversely when the two drugs were coadministered. The purpose of this study was to investigate the presence of differences in the pharmacokinetic profiles of capsules containing atorvastatin 80 mg, ezetimibe 10 mg or the combination of both 80/10 mg administered to healthy Mexican volunteers. This was a randomized, three-period, six-sequences crossover study. 36 eligible subjects aged between 20 to 50 years were included. Blood samples were collected up to 96 h after dosing, and pharmacokinetic parameters were obtained by noncompartmental analysis. Adverse events were evaluated based on subject interviews and physical examinations. Area under the concentration-time curve (AUC) and maximum plasma drug concentration (Cmax) were measured for each drug alone or together and tested for bioequivalencebased hypothesis. The estimation computed (90{\%} confidence intervals) for AUC and Cmax, were 96.04{\%} (85.88{\%}-107.42{\%}) and 97.04{\%} (82.36{\%}-114.35{\%}), respectively for atorvastatin-ezetimibe combination versus atorvastatin alone, while 84.42{\%} (77.19{\%}-92.32{\%}) and 95.60{\%} (82.43{\%}- 110.88{\%}), respectively, for atorvastatin-ezetimibe combination versus ezetimibe alone were estimated. These results suggest that atorvastatin and ezetimibe have no relevant pharmacokinetic drug-drug interaction.",
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Pharmacokinetic non-interaction analysis in a fixed-dose formulation in combination of atorvastatin and ezetimibe. / Omar, Patiño Rodríguez; Irma, Torres Roque; Maricela, Martínez Delgado; Abraham, Escobedo Moratilla; José, Pérez Urizar.

In: Frontiers in Pharmacology, 01.01.2014.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pharmacokinetic non-interaction analysis in a fixed-dose formulation in combination of atorvastatin and ezetimibe

AU - Omar, Patiño Rodríguez

AU - Irma, Torres Roque

AU - Maricela, Martínez Delgado

AU - Abraham, Escobedo Moratilla

AU - José, Pérez Urizar

PY - 2014/1/1

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N2 - © 2014 Patiño-rodríguez, Torres-roque, Martínez-delgado, Escobedo-moratilla and Pérez-urizar. Recent clinical research has shown that atorvastatin in combination with cholesterol absorption inhibitor ezetimibe significantly reduces LDL-C level in patients with hypercholesterolemia, showing a superior lipid-lowering efficacy compared to statin alone. With no information currently available on the interaction between the two drugs, a pharmacokinetic study was conducted to investigate the influence of ezetimibe on atorvastatin and conversely when the two drugs were coadministered. The purpose of this study was to investigate the presence of differences in the pharmacokinetic profiles of capsules containing atorvastatin 80 mg, ezetimibe 10 mg or the combination of both 80/10 mg administered to healthy Mexican volunteers. This was a randomized, three-period, six-sequences crossover study. 36 eligible subjects aged between 20 to 50 years were included. Blood samples were collected up to 96 h after dosing, and pharmacokinetic parameters were obtained by noncompartmental analysis. Adverse events were evaluated based on subject interviews and physical examinations. Area under the concentration-time curve (AUC) and maximum plasma drug concentration (Cmax) were measured for each drug alone or together and tested for bioequivalencebased hypothesis. The estimation computed (90% confidence intervals) for AUC and Cmax, were 96.04% (85.88%-107.42%) and 97.04% (82.36%-114.35%), respectively for atorvastatin-ezetimibe combination versus atorvastatin alone, while 84.42% (77.19%-92.32%) and 95.60% (82.43%- 110.88%), respectively, for atorvastatin-ezetimibe combination versus ezetimibe alone were estimated. These results suggest that atorvastatin and ezetimibe have no relevant pharmacokinetic drug-drug interaction.

AB - © 2014 Patiño-rodríguez, Torres-roque, Martínez-delgado, Escobedo-moratilla and Pérez-urizar. Recent clinical research has shown that atorvastatin in combination with cholesterol absorption inhibitor ezetimibe significantly reduces LDL-C level in patients with hypercholesterolemia, showing a superior lipid-lowering efficacy compared to statin alone. With no information currently available on the interaction between the two drugs, a pharmacokinetic study was conducted to investigate the influence of ezetimibe on atorvastatin and conversely when the two drugs were coadministered. The purpose of this study was to investigate the presence of differences in the pharmacokinetic profiles of capsules containing atorvastatin 80 mg, ezetimibe 10 mg or the combination of both 80/10 mg administered to healthy Mexican volunteers. This was a randomized, three-period, six-sequences crossover study. 36 eligible subjects aged between 20 to 50 years were included. Blood samples were collected up to 96 h after dosing, and pharmacokinetic parameters were obtained by noncompartmental analysis. Adverse events were evaluated based on subject interviews and physical examinations. Area under the concentration-time curve (AUC) and maximum plasma drug concentration (Cmax) were measured for each drug alone or together and tested for bioequivalencebased hypothesis. The estimation computed (90% confidence intervals) for AUC and Cmax, were 96.04% (85.88%-107.42%) and 97.04% (82.36%-114.35%), respectively for atorvastatin-ezetimibe combination versus atorvastatin alone, while 84.42% (77.19%-92.32%) and 95.60% (82.43%- 110.88%), respectively, for atorvastatin-ezetimibe combination versus ezetimibe alone were estimated. These results suggest that atorvastatin and ezetimibe have no relevant pharmacokinetic drug-drug interaction.

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M3 - Article

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SN - 1663-9812

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