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Bioequivalence of a single 10-mg dose of finasteride 5-mg oral disintegrating tablets and standard tablets in healthy adult male Han Chinese volunteers: A randomized sequence, open-label, two-way crossover study

Abstract Background: Finasteride, an inhibitor of the steroid 5α-reductase, has been approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia. An orally disintegrating tablet (ODT) 5-mg formulation of finasteride was recently developed. Information regarding its pharmacok... Full description

Journal Title: Clinical therapeutics 2009, Vol.31 (10), p.2242-2248
Main Author: Chen, Li, MD
Other Authors: Jiang, Xuehua, PhD , Huang, Liang, MD , Lan, Ke, PhD , Wang, Haiying, MD , Hu, Lina, MD , Ren, Jing, PhD , Li, Xihong, PhD , Zou, Qin, MD
Format: Electronic Article Electronic Article
Language: English
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Quelle: Alma/SFX Local Collection
Publisher: Bridgewater, NJ: EM Inc USA
ID: ISSN: 0149-2918
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title: Bioequivalence of a single 10-mg dose of finasteride 5-mg oral disintegrating tablets and standard tablets in healthy adult male Han Chinese volunteers: A randomized sequence, open-label, two-way crossover study
format: Article
creator:
  • Chen, Li, MD
  • Jiang, Xuehua, PhD
  • Huang, Liang, MD
  • Lan, Ke, PhD
  • Wang, Haiying, MD
  • Hu, Lina, MD
  • Ren, Jing, PhD
  • Li, Xihong, PhD
  • Zou, Qin, MD
subjects:
  • Adults
  • Analysis
  • Antiandrogens
  • Area Under Curve
  • bioavailability
  • bioequivalence
  • Biological and medical sciences
  • Chromatography, High Pressure Liquid
  • Cross-Over Studies
  • Enzyme Inhibitors - administration & dosage
  • Enzyme Inhibitors - adverse effects
  • Enzyme Inhibitors - pharmacokinetics
  • Finasteride
  • Finasteride - administration & dosage
  • Finasteride - adverse effects
  • Finasteride - pharmacokinetics
  • Half-Life
  • human
  • Humans
  • Internal Medicine
  • Male
  • Mass Spectrometry
  • Medical Education
  • Medical sciences
  • pharmacokinetics
  • Pharmacology. Drug treatments
  • Safety regulations
  • Solubility
  • Standards
  • Tablets
  • Therapeutic Equivalency
  • Urine
  • Young Adult
ispartof: Clinical therapeutics, 2009, Vol.31 (10), p.2242-2248
description: Abstract Background: Finasteride, an inhibitor of the steroid 5α-reductase, has been approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia. An orally disintegrating tablet (ODT) 5-mg formulation of finasteride was recently developed. Information regarding its pharmacokinetics and bioequivalence was required to assess the efficacy and safety of this formulation before marketing it in China. Objectives: The aims of this study were to compare the bioavailability of finasteride ODTs and standard tablets in healthy adult male Han Chinese volunteers and to determine whether any observed differences exceeded Chinese regulatory guidelines for bioequivalence. Methods: This single-dose, randomized, open-label, 2-way crossover trial was conducted in China. Healthy adult male Han Chinese volunteers were enrolled. Participants were randomly assigned to receive 10 mg of either the ODT or standard tablet formulation, followed by a 1-week washout period and administration of the alternate formulation. Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties, including Cmax , AUC0–24 , and AUC0–∞ , blood samples were obtained at 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 5, 8, 11, 14, and 24 hours after administration. The formulations were to be considered bioequivalent if calculations of the 90% CI for the ratio of the means of the measures for the test and reference formulations fell within bioequivalence limits, 80% to 125%, for logarithmic (log) transformation of Cmax and AUC, and if Schuirmann's two 1-sided tests showed P < 0.05. Tolerability was assessed using vital sign measurements (ie, blood pressure, body temperature, heart rate, and respiratory rate), laboratory analysis (ie, he-2242 matology, blood biochemistry, hepatic function, and urinalysis), and interviews with participants. Results: Twenty-four men (mean [SD] age, 22.0 [1.2] years [range, 20–24 years]; weight, 63.5 [4.6] kg [range, 55–70 kg]; height, 172.8 [4.4] cm [range, 164–180 cm]) were enrolled in this study, and 24 (12 each randomized to receive the ODT or standard tablet first) completed it. No period or sequence effects were observed. The 90% CIs for the log-transformed Cmax , AUC0–24 , and AUC0–∞ values were 86.8 to 106.8, 95.1 to 119.1, and 96.2 to 117.5, respectively (all, P < 0.05). The Wilcoxon rank sum test of Tmax found a significant difference between the ODT formulation (mean [SD], 2.40 [0.47] hours) and standard tablet formulat
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0149-2918
fulltext: fulltext
issn:
  • 0149-2918
  • 1879-114X
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titleBioequivalence of a single 10-mg dose of finasteride 5-mg oral disintegrating tablets and standard tablets in healthy adult male Han Chinese volunteers: A randomized sequence, open-label, two-way crossover study
sourceAlma/SFX Local Collection
creatorChen, Li, MD ; Jiang, Xuehua, PhD ; Huang, Liang, MD ; Lan, Ke, PhD ; Wang, Haiying, MD ; Hu, Lina, MD ; Ren, Jing, PhD ; Li, Xihong, PhD ; Zou, Qin, MD
creatorcontribChen, Li, MD ; Jiang, Xuehua, PhD ; Huang, Liang, MD ; Lan, Ke, PhD ; Wang, Haiying, MD ; Hu, Lina, MD ; Ren, Jing, PhD ; Li, Xihong, PhD ; Zou, Qin, MD
descriptionAbstract Background: Finasteride, an inhibitor of the steroid 5α-reductase, has been approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia. An orally disintegrating tablet (ODT) 5-mg formulation of finasteride was recently developed. Information regarding its pharmacokinetics and bioequivalence was required to assess the efficacy and safety of this formulation before marketing it in China. Objectives: The aims of this study were to compare the bioavailability of finasteride ODTs and standard tablets in healthy adult male Han Chinese volunteers and to determine whether any observed differences exceeded Chinese regulatory guidelines for bioequivalence. Methods: This single-dose, randomized, open-label, 2-way crossover trial was conducted in China. Healthy adult male Han Chinese volunteers were enrolled. Participants were randomly assigned to receive 10 mg of either the ODT or standard tablet formulation, followed by a 1-week washout period and administration of the alternate formulation. Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties, including Cmax , AUC0–24 , and AUC0–∞ , blood samples were obtained at 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 5, 8, 11, 14, and 24 hours after administration. The formulations were to be considered bioequivalent if calculations of the 90% CI for the ratio of the means of the measures for the test and reference formulations fell within bioequivalence limits, 80% to 125%, for logarithmic (log) transformation of Cmax and AUC, and if Schuirmann's two 1-sided tests showed P < 0.05. Tolerability was assessed using vital sign measurements (ie, blood pressure, body temperature, heart rate, and respiratory rate), laboratory analysis (ie, he-2242 matology, blood biochemistry, hepatic function, and urinalysis), and interviews with participants. Results: Twenty-four men (mean [SD] age, 22.0 [1.2] years [range, 20–24 years]; weight, 63.5 [4.6] kg [range, 55–70 kg]; height, 172.8 [4.4] cm [range, 164–180 cm]) were enrolled in this study, and 24 (12 each randomized to receive the ODT or standard tablet first) completed it. No period or sequence effects were observed. The 90% CIs for the log-transformed Cmax , AUC0–24 , and AUC0–∞ values were 86.8 to 106.8, 95.1 to 119.1, and 96.2 to 117.5, respectively (all, P < 0.05). The Wilcoxon rank sum test of Tmax found a significant difference between the ODT formulation (mean [SD], 2.40 [0.47] hours) and standard tablet formulation (1.98 [0.63] hours). No adverse events were reported by the volunteers or found in clinical laboratory testing during the study. Conclusions: In this single-dose study, based on the rate and extent of absorption, the ODT (ie, test) and standard tablet (ie, reference) formulations of finasteride met the regulatory criteria for bioequivalence in these fasting healthy adult male Han Chinese volunteers. However, a significant difference was found for Tmax between the test and reference formulations. Both formulations were well tolerated. ClinicalTrials. gov identifier: 2005L02216
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subjectAdults ; Analysis ; Antiandrogens ; Area Under Curve ; bioavailability ; bioequivalence ; Biological and medical sciences ; Chromatography, High Pressure Liquid ; Cross-Over Studies ; Enzyme Inhibitors - administration & dosage ; Enzyme Inhibitors - adverse effects ; Enzyme Inhibitors - pharmacokinetics ; Finasteride ; Finasteride - administration & dosage ; Finasteride - adverse effects ; Finasteride - pharmacokinetics ; Half-Life ; human ; Humans ; Internal Medicine ; Male ; Mass Spectrometry ; Medical Education ; Medical sciences ; pharmacokinetics ; Pharmacology. Drug treatments ; Safety regulations ; Solubility ; Standards ; Tablets ; Therapeutic Equivalency ; Urine ; Young Adult
ispartofClinical therapeutics, 2009, Vol.31 (10), p.2242-2248
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0Chen, Li, MD
1Jiang, Xuehua, PhD
2Huang, Liang, MD
3Lan, Ke, PhD
4Wang, Haiying, MD
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7Li, Xihong, PhD
8Zou, Qin, MD
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1Clinical therapeutics
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descriptionAbstract Background: Finasteride, an inhibitor of the steroid 5α-reductase, has been approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia. An orally disintegrating tablet (ODT) 5-mg formulation of finasteride was recently developed. Information regarding its pharmacokinetics and bioequivalence was required to assess the efficacy and safety of this formulation before marketing it in China. Objectives: The aims of this study were to compare the bioavailability of finasteride ODTs and standard tablets in healthy adult male Han Chinese volunteers and to determine whether any observed differences exceeded Chinese regulatory guidelines for bioequivalence. Methods: This single-dose, randomized, open-label, 2-way crossover trial was conducted in China. Healthy adult male Han Chinese volunteers were enrolled. Participants were randomly assigned to receive 10 mg of either the ODT or standard tablet formulation, followed by a 1-week washout period and administration of the alternate formulation. Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties, including Cmax , AUC0–24 , and AUC0–∞ , blood samples were obtained at 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 5, 8, 11, 14, and 24 hours after administration. The formulations were to be considered bioequivalent if calculations of the 90% CI for the ratio of the means of the measures for the test and reference formulations fell within bioequivalence limits, 80% to 125%, for logarithmic (log) transformation of Cmax and AUC, and if Schuirmann's two 1-sided tests showed P < 0.05. Tolerability was assessed using vital sign measurements (ie, blood pressure, body temperature, heart rate, and respiratory rate), laboratory analysis (ie, he-2242 matology, blood biochemistry, hepatic function, and urinalysis), and interviews with participants. Results: Twenty-four men (mean [SD] age, 22.0 [1.2] years [range, 20–24 years]; weight, 63.5 [4.6] kg [range, 55–70 kg]; height, 172.8 [4.4] cm [range, 164–180 cm]) were enrolled in this study, and 24 (12 each randomized to receive the ODT or standard tablet first) completed it. No period or sequence effects were observed. The 90% CIs for the log-transformed Cmax , AUC0–24 , and AUC0–∞ values were 86.8 to 106.8, 95.1 to 119.1, and 96.2 to 117.5, respectively (all, P < 0.05). The Wilcoxon rank sum test of Tmax found a significant difference between the ODT formulation (mean [SD], 2.40 [0.47] hours) and standard tablet formulation (1.98 [0.63] hours). No adverse events were reported by the volunteers or found in clinical laboratory testing during the study. Conclusions: In this single-dose study, based on the rate and extent of absorption, the ODT (ie, test) and standard tablet (ie, reference) formulations of finasteride met the regulatory criteria for bioequivalence in these fasting healthy adult male Han Chinese volunteers. However, a significant difference was found for Tmax between the test and reference formulations. Both formulations were well tolerated. ClinicalTrials. gov identifier: 2005L02216
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22Medical Education
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24pharmacokinetics
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titleBioequivalence of a single 10-mg dose of finasteride 5-mg oral disintegrating tablets and standard tablets in healthy adult male Han Chinese volunteers: A randomized sequence, open-label, two-way crossover study
authorChen, Li, MD ; Jiang, Xuehua, PhD ; Huang, Liang, MD ; Lan, Ke, PhD ; Wang, Haiying, MD ; Hu, Lina, MD ; Ren, Jing, PhD ; Li, Xihong, PhD ; Zou, Qin, MD
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abstractAbstract Background: Finasteride, an inhibitor of the steroid 5α-reductase, has been approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia. An orally disintegrating tablet (ODT) 5-mg formulation of finasteride was recently developed. Information regarding its pharmacokinetics and bioequivalence was required to assess the efficacy and safety of this formulation before marketing it in China. Objectives: The aims of this study were to compare the bioavailability of finasteride ODTs and standard tablets in healthy adult male Han Chinese volunteers and to determine whether any observed differences exceeded Chinese regulatory guidelines for bioequivalence. Methods: This single-dose, randomized, open-label, 2-way crossover trial was conducted in China. Healthy adult male Han Chinese volunteers were enrolled. Participants were randomly assigned to receive 10 mg of either the ODT or standard tablet formulation, followed by a 1-week washout period and administration of the alternate formulation. Doses were administered after a 12-hour overnight fast. For analysis of pharmacokinetic properties, including Cmax , AUC0–24 , and AUC0–∞ , blood samples were obtained at 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 5, 8, 11, 14, and 24 hours after administration. The formulations were to be considered bioequivalent if calculations of the 90% CI for the ratio of the means of the measures for the test and reference formulations fell within bioequivalence limits, 80% to 125%, for logarithmic (log) transformation of Cmax and AUC, and if Schuirmann's two 1-sided tests showed P < 0.05. Tolerability was assessed using vital sign measurements (ie, blood pressure, body temperature, heart rate, and respiratory rate), laboratory analysis (ie, he-2242 matology, blood biochemistry, hepatic function, and urinalysis), and interviews with participants. Results: Twenty-four men (mean [SD] age, 22.0 [1.2] years [range, 20–24 years]; weight, 63.5 [4.6] kg [range, 55–70 kg]; height, 172.8 [4.4] cm [range, 164–180 cm]) were enrolled in this study, and 24 (12 each randomized to receive the ODT or standard tablet first) completed it. No period or sequence effects were observed. The 90% CIs for the log-transformed Cmax , AUC0–24 , and AUC0–∞ values were 86.8 to 106.8, 95.1 to 119.1, and 96.2 to 117.5, respectively (all, P < 0.05). The Wilcoxon rank sum test of Tmax found a significant difference between the ODT formulation (mean [SD], 2.40 [0.47] hours) and standard tablet formulation (1.98 [0.63] hours). No adverse events were reported by the volunteers or found in clinical laboratory testing during the study. Conclusions: In this single-dose study, based on the rate and extent of absorption, the ODT (ie, test) and standard tablet (ie, reference) formulations of finasteride met the regulatory criteria for bioequivalence in these fasting healthy adult male Han Chinese volunteers. However, a significant difference was found for Tmax between the test and reference formulations. Both formulations were well tolerated. ClinicalTrials. gov identifier: 2005L02216
copBridgewater, NJ
pubEM Inc USA
pmid19922895
doi10.1016/j.clinthera.2009.09.015