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Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: a single-dose and two-period crossover randomized study.

ABSTRACT: BACKGROUND:Levamlodipine, a calcium channel blocker, has been show act as a cardiovascular drug. To compare the pharmacokinetic parameters between levamlodipine (test formulation) at a single dose of 5?mg and amlodipine (reference formulation) at a single dose of 10?mg, the bioequivalence study was carried out. METHODS:A single-dose randomized, open-label, two-period crossover study was designed in healthy Chinese subjects. 48 subjects were divided into fasted and fed groups equally. The subjects randomly received the test or reference formulations at the rate of 1:1. Following a 21-day washout period, the alternative formulations were received. The blood samples were collected at 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 24, 36, 48, 72, 96, 120, 144, 168?h later. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine the plasma concentrations of levamlodipine. Adverse events were recorded. RESULTS:The 90% confidence intervals (CIs) of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-? under both fasted and fed conditions were within the prespecified bioequivalence limits between 80?~?125%. Under fasted conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.70?±?0.49) ng/mL, AUC0-t was (141.32?±?36.24) ng?×?h/mL and AUC0-? was (157.14?±?45.65) ng?×?h/mL after a single dose of 5?mg levamlodipine. The mean Cmax was (2.83?±?0.52) ng/mL, AUC0-t was (153.62?±?33.96) ng?×?h/mL and AUC0-? was (173.05?±?41.78) ng?×?h/mL after a single dose of 10?mg amlodipine. Under fed conditions, 24 subjects were enrolled and completed the study. The mean Cmax was (2.73?±?0.55) ng/mL, AUC0-t was (166.93?±?49.96) ng?×?h/mL and AUC0-? was (190.99?±?70.89) ng?×?h/mL after a single dose of 5?mg levamlodipine. The mean Cmax was (2.87?±?0.81) ng/mL AUC0-t was (165.46?±?43.58) ng?×?h/mL and AUC0-? was (189.51?±?64.70) ng?×?h/mL after a single dose of 10?mg amlodipine. Serious adverse event was not observed. CONCLUSION:The trial confirmed that levamlodipine at a single dose of 5?mg and amlodipine at a single dose of 10?mg were bioequivalent under both fasted condition and fed condition. TRIAL REGISTRATION:Cinicaltrials, NCT04411875 . Registered 3 June 2020 - Retrospectively registered.

SUBMITTER: Li X

PROVIDER: S-EPMC7678077 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: a single-dose and two-period crossover randomized study.

Li Xin X Wang Chenjing C Li Ting T Liu Yanping Y Liu Shuqin S Tao Ye Y Ma Yaping Y Gao Xiaomeng X Cao Yu Y

BMC pharmacology & toxicology 20201119 1

<h4>Background</h4>Levamlodipine, a calcium channel blocker, has been show act as a cardiovascular drug. To compare the pharmacokinetic parameters between levamlodipine (test formulation) at a single dose of 5 mg and amlodipine (reference formulation) at a single dose of 10 mg, the bioequivalence study was carried out.<h4>Methods</h4>A single-dose randomized, open-label, two-period crossover study was designed in healthy Chinese subjects. 48 subjects were divided into fasted and fed groups equal ...[more]

PMID: 33213527

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Project description:BackgroundA fixed-dose combination (FDC) of amlodipine and losartan has been used to reduce blood pressure in patients whose hypertension is not sufficiently controlled with either drug alone. The aim of this study was to evaluate the pharmacokinetic (PK) characteristics and tolerability of an FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium compared to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium in healthy subjects.Subjects and methodsA randomized, open-label, single-dose, two-period, two-sequence crossover study was conducted on 46 healthy male subjects. Blood concentrations were measured by liquid chromatography-tandem mass spectrometry. Blood samples were collected up to 144 hours post dose for each period. PK parameters were calculated in each treatment group using a noncompartmental method. The 90% confidence intervals (CIs) of the geometric mean ratios of the two treatments for the maximum plasma concentration (Cmax) and the area under the concentration curve from time zero to the last quantifiable time point (AUC0-t) were estimated. Tolerability assessments were performed for all subjects who received the drug at least once.ResultsThe PK profiles of the two treatments were similar. For amlodipine, the geometric mean ratios (90% CIs) of amlodipine besylate to amlodipine camsylate for the Cmax and AUC0-t were 0.98 (0.94-1.01) and 0.97 (0.93-1.01), respectively. The corresponding values for losartan were 0.91 (0.81-1.02) and 1.05 (0.98-1.12), respectively. The incidence of adverse events was not significantly different between the two treatments, and both were well tolerated.ConclusionAn FDC of 6.94 mg amlodipine besylate (5 mg as amlodipine)/50 mg losartan potassium produced similar results to an FDC of 5 mg amlodipine camsylate/50 mg losartan potassium treatment with respect to the PK parameters of amlodipine and losartan based on Cmax and AUC0-t values. The amlodipine besylate/losartan potassium combination was well tolerated by healthy male subjects.

Project description:BackgroundEzetimibe is a new class of antihyperlipidemic agent indicated for the prevention of atherosclerosis disease and for the treatment of hypercholesterolemia. Information on the pharmacokinetic profiles of ezetimibe tablet in healthy Chinese volunteers are lacking, and regulatory requirements necessitate a bioequivalence study of ezetimibe tablet versus Ezetrol® in China.MethodsA single-dose randomized, open-label, two-group, two-period crossover study was conducted in 59 healthy Chinese volunteers under fasting or fed conditions to assess the bioequivalence between two preparations. Eligible participants were randomly divided into fasted and fed groups. Blood samples were collected at specified time intervals, and the plasma concentrations of ezetimibe and ezetimibe glucuronide were determined by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. PK and bioavailability parameters were estimated via non-compartmental methods. Adverse events were also recorded.ResultsFifty-nine healthy volunteers were enrolled in the study. The main pharmacokinetic parameters of total ezetimibe in the plasma of the ezetimibe tablet (10 mg) and the Ezetrol® (10 mg) after a single fasting administration: Cmax were (65.73 ± 47.14), (71.32 ± 51.98) ng·mL- 1; Tmax were 1.75, 1.25 h; T½ were (17.09 ± 13.22), (17.35 ± 12.14) h; AUC0-t were (643.34 ± 400.77), (668.49 ± 439.57) h·ng·mL- 1; AUC0-∞ were (706.36 ± 410.92), (734.23 ± 468.26) h·ng·mL- 1. The main pharmacokinetic parameters of total ezetimibe in plasma of ezetimibe tablet (10 mg) and Ezetrol® (10 mg) after a fed administration: Cmax were (83.38 ± 38.95), (84.74 ± 34.62) ng·mL- 1; Tmax were 2.50, 2.50 h; T½ were (22.56 ± 12.68), (19.80 ± 15.59) h; AUC0-t were (494.21 ± 208.65), (536.69 ± 209.11) h·ng·mL- 1; AUC0-∞ were (573.74 ± 252.74), (604.75 ± 247.13) h·ng·mL- 1. The main pharmacokinetic parameters Cmax, AUC0-t, and AUC0-∞ of the two drugs were analyzed by variance analysis after logarithmic transformation. The total ezetimibe under fasting state with 90% confidence intervals (CIs) were 85.29 ~ 97.19, 90.41% ~ 104.38%, and 90.81 ~ 106.05%; total ezetimibe in fed state were 86.36% ~ 109.17, 84.96% ~ 96.40, and 85.32% ~ 101.0%. The 90% CIs of the ratio of geometric means (GMRs) of Cmax, AUC0-t, and AUC0-∞ of Ezetrol® and ezetimibe tablet both fasting and fed conditions fell within the conventional bioequivalence criteria of 0.80-1.25. Both Cmax and AUC met the predetermined criteria for assuming bioequivalence. No severe adverse events were observed.ConclusionsThe test ezetimibe tablet and Ezetrol® were determined to be bioequivalent under both fasting and fed conditions in Chinese people.Trial registrationClinicaltrials, NCT05681247 (retrospectively registered in 11/01/ 2023).

Project description:UnlabelledThe present study aimed to investigate the pharmacokinetic properties of febuxostat in healthy Chinese male volunteers and evaluate whether the two formulations of febuxostat 40-mg and 80-mg tablets are bioequivalent. A randomized, open-label, 4-way crossover study was conducted in healthy Chinese male volunteers under fasting conditions. 24 eligible subjects were randomized in a 1:1:1:1 ratio to receive a single dose of test or reference formulation of febuxostat 40-mg or 80-mg tablet. The washout period between each administration was 1 week. Plasma febuxostat was quantified by a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Tolerability was evaluated by monitoring adverse events, physical examinations, 12-lead ECG and laboratory tests. After single-dosing of 1 tablet of 40-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.22±0.87 and 1.85±1.03 h, Cmax 1689.16±461.31 and 1613.80±608.43 ng·mL-1, AUC0-t 5139.87±1349.28 and 5517.91±2024.26 ng·mL-1·h, AUC0-∞ 5263.06±1339.16 and 5640.48±2040.22 ng·mL-1·h, t1/2 4.82±2.61 and 4.85±1.78 h, respectively. After single-dosing of 1 tablet of 80-mg febuxostat, the pharmacokinetic parameters of test and reference formulations were: Tmax 1.71±1.21 and 2.23±1.55 h, Cmax 2744.47±1157.44 and 2998.17±1200.13 ng·mL-1, AUC0-t 9634.03±2768.25 and 10467.95±3501.65 ng·mL-1·h, AUC0-∞ 9834.32±2730.51 and 10626.63±3504.08 ng·mL-1·h, t1/2 6.25±2.44 and 5.46±1.65 h, respectively. For single-dosing of 1 tablet of 40-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0-∞ and Cmax were 89.79 to 102.55, 90.14 to 102.56 and 93.99 to 129.63, respectively. For single-dosing of 1 tablet of 80-mg febuxostat, 90% CIs for the test/reference ratio of AUC0-t, AUC0-∞ and Cmax were 86.67 to 100.00, 87.50 to 100.51 and 79.48 to 105.99, respectively. This single dose study revealed similar pharmacokinetic properties in healthy Chinese male volunteers as those found in Caucasic population. The test and reference febuxostat tablets formulations met the regulatory criteria for bioequivalence at 40-mg and 80-mg strengths in fasting healthy Chinese male volunteers.Trial registrationChictr.org ChiCTR-TTRCC-14004288.

Dataset Information

Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: a single-dose and two-period crossover randomized study.

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Bioequivalence of levamlodipine besylate tablets in healthy Chinese subjects: a single-dose and two-period crossover randomized study.

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