Pharmacokinetics and tolerability of probucol after multiple oral administration in healthy volunteers

H. Jeon, S. Lee, T. E. Kim, S. H. Yoon, S. G. Shin, I. J. Jang, K. S. Yu

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Probucol is indicated for primary hyperlipidemia and for hypercholesterolemia with hypertriglyceridemia. The objective of this study was to evaluate the tolerability and pharmacokinetics of probucol by multiple oral administration in healthy Korean male subjects. Methods: This study was conducted by a randomized, open-label, three-treatment, parallel-group design. A total of 30 subjects were randomly assigned to 1 of the 3 treatment groups were administered probucol orally at 250 mg once daily (q.d.) after breakfast (250 mg/d), at 500 mg once daily after breakfast (500 mg/d), or at 250 mg twice a day (b.i.d) after breakfast and dinner (500 mg/d) for 14 days. Serial samples of blood were collected and plasma drug concentrations were determined using liquid chromatography-tandem mass spectrometry (LC/MS/MS). For tolerability assessment, measurement of vital signs and electrocardiograms (ECG), clinical laboratory tests and physical examinations were performed. Results: At Day 13, the mean of the AUC 24h of probucol was 123,800 μg x h/l in the 250 mg q.d. group, 198,500 μg x h/l in the 500 mg q.d. group, and 244,700 μg x h/l in the 250 mg b.i.d. group. The mean accumulation index for AUC 24h (ratio of AUC 24h for Day 13 to that for Day 1) was 2.5 in the 250 mg QD group, 2.85 in the 500 mg QD group, and 4.21 in the 250 mg b.i.d. group. No clinically significant changes in ECG, including QTc prolongation were observed during the study period. All adverse events were mild and no clinically significant changes were observed in any other tolerability assessment, thus confirming tolerability for all regimens tested. Conclusions: This study provided data on the pharmacokinetics and tolerability of probucol by multiple oral administrations in healthy male volunteers.

Original languageEnglish
Pages (from-to)688-694
Number of pages7
JournalInternational Journal of Clinical Pharmacology and Therapeutics
Volume49
Issue number11
DOIs
StatePublished - 1 Nov 2011

Fingerprint

Probucol
Breakfast
Oral Administration
Healthy Volunteers
Pharmacokinetics
Area Under Curve
Electrocardiography
Vital Signs
Hypertriglyceridemia
Tandem Mass Spectrometry
Hypercholesterolemia
Hyperlipidemias
Liquid Chromatography
Physical Examination
Meals
Therapeutics
Pharmaceutical Preparations

Keywords

  • Accumulation index
  • Multiple administrations
  • Pharmacokinetics
  • Probucol
  • Tolerability

Cite this

@article{ba6370d821454db1a681fff64d3d673d,
title = "Pharmacokinetics and tolerability of probucol after multiple oral administration in healthy volunteers",
abstract = "Background: Probucol is indicated for primary hyperlipidemia and for hypercholesterolemia with hypertriglyceridemia. The objective of this study was to evaluate the tolerability and pharmacokinetics of probucol by multiple oral administration in healthy Korean male subjects. Methods: This study was conducted by a randomized, open-label, three-treatment, parallel-group design. A total of 30 subjects were randomly assigned to 1 of the 3 treatment groups were administered probucol orally at 250 mg once daily (q.d.) after breakfast (250 mg/d), at 500 mg once daily after breakfast (500 mg/d), or at 250 mg twice a day (b.i.d) after breakfast and dinner (500 mg/d) for 14 days. Serial samples of blood were collected and plasma drug concentrations were determined using liquid chromatography-tandem mass spectrometry (LC/MS/MS). For tolerability assessment, measurement of vital signs and electrocardiograms (ECG), clinical laboratory tests and physical examinations were performed. Results: At Day 13, the mean of the AUC 24h of probucol was 123,800 μg x h/l in the 250 mg q.d. group, 198,500 μg x h/l in the 500 mg q.d. group, and 244,700 μg x h/l in the 250 mg b.i.d. group. The mean accumulation index for AUC 24h (ratio of AUC 24h for Day 13 to that for Day 1) was 2.5 in the 250 mg QD group, 2.85 in the 500 mg QD group, and 4.21 in the 250 mg b.i.d. group. No clinically significant changes in ECG, including QTc prolongation were observed during the study period. All adverse events were mild and no clinically significant changes were observed in any other tolerability assessment, thus confirming tolerability for all regimens tested. Conclusions: This study provided data on the pharmacokinetics and tolerability of probucol by multiple oral administrations in healthy male volunteers.",
keywords = "Accumulation index, Multiple administrations, Pharmacokinetics, Probucol, Tolerability",
author = "H. Jeon and S. Lee and Kim, {T. E.} and Yoon, {S. H.} and Shin, {S. G.} and Jang, {I. J.} and Yu, {K. S.}",
year = "2011",
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pages = "688--694",
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TY - JOUR

T1 - Pharmacokinetics and tolerability of probucol after multiple oral administration in healthy volunteers

AU - Jeon, H.

AU - Lee, S.

AU - Kim, T. E.

AU - Yoon, S. H.

AU - Shin, S. G.

AU - Jang, I. J.

AU - Yu, K. S.

PY - 2011/11/1

Y1 - 2011/11/1

N2 - Background: Probucol is indicated for primary hyperlipidemia and for hypercholesterolemia with hypertriglyceridemia. The objective of this study was to evaluate the tolerability and pharmacokinetics of probucol by multiple oral administration in healthy Korean male subjects. Methods: This study was conducted by a randomized, open-label, three-treatment, parallel-group design. A total of 30 subjects were randomly assigned to 1 of the 3 treatment groups were administered probucol orally at 250 mg once daily (q.d.) after breakfast (250 mg/d), at 500 mg once daily after breakfast (500 mg/d), or at 250 mg twice a day (b.i.d) after breakfast and dinner (500 mg/d) for 14 days. Serial samples of blood were collected and plasma drug concentrations were determined using liquid chromatography-tandem mass spectrometry (LC/MS/MS). For tolerability assessment, measurement of vital signs and electrocardiograms (ECG), clinical laboratory tests and physical examinations were performed. Results: At Day 13, the mean of the AUC 24h of probucol was 123,800 μg x h/l in the 250 mg q.d. group, 198,500 μg x h/l in the 500 mg q.d. group, and 244,700 μg x h/l in the 250 mg b.i.d. group. The mean accumulation index for AUC 24h (ratio of AUC 24h for Day 13 to that for Day 1) was 2.5 in the 250 mg QD group, 2.85 in the 500 mg QD group, and 4.21 in the 250 mg b.i.d. group. No clinically significant changes in ECG, including QTc prolongation were observed during the study period. All adverse events were mild and no clinically significant changes were observed in any other tolerability assessment, thus confirming tolerability for all regimens tested. Conclusions: This study provided data on the pharmacokinetics and tolerability of probucol by multiple oral administrations in healthy male volunteers.

AB - Background: Probucol is indicated for primary hyperlipidemia and for hypercholesterolemia with hypertriglyceridemia. The objective of this study was to evaluate the tolerability and pharmacokinetics of probucol by multiple oral administration in healthy Korean male subjects. Methods: This study was conducted by a randomized, open-label, three-treatment, parallel-group design. A total of 30 subjects were randomly assigned to 1 of the 3 treatment groups were administered probucol orally at 250 mg once daily (q.d.) after breakfast (250 mg/d), at 500 mg once daily after breakfast (500 mg/d), or at 250 mg twice a day (b.i.d) after breakfast and dinner (500 mg/d) for 14 days. Serial samples of blood were collected and plasma drug concentrations were determined using liquid chromatography-tandem mass spectrometry (LC/MS/MS). For tolerability assessment, measurement of vital signs and electrocardiograms (ECG), clinical laboratory tests and physical examinations were performed. Results: At Day 13, the mean of the AUC 24h of probucol was 123,800 μg x h/l in the 250 mg q.d. group, 198,500 μg x h/l in the 500 mg q.d. group, and 244,700 μg x h/l in the 250 mg b.i.d. group. The mean accumulation index for AUC 24h (ratio of AUC 24h for Day 13 to that for Day 1) was 2.5 in the 250 mg QD group, 2.85 in the 500 mg QD group, and 4.21 in the 250 mg b.i.d. group. No clinically significant changes in ECG, including QTc prolongation were observed during the study period. All adverse events were mild and no clinically significant changes were observed in any other tolerability assessment, thus confirming tolerability for all regimens tested. Conclusions: This study provided data on the pharmacokinetics and tolerability of probucol by multiple oral administrations in healthy male volunteers.

KW - Accumulation index

KW - Multiple administrations

KW - Pharmacokinetics

KW - Probucol

KW - Tolerability

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U2 - 10.5414/CP201525

DO - 10.5414/CP201525

M3 - Article

C2 - 22011694

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JO - International Journal of Clinical Pharmacology and Therapeutics

JF - International Journal of Clinical Pharmacology and Therapeutics

SN - 0946-1965

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