Pharmacokinetics and Safety of Single-Dose Amphotericin B Colloidal Dispersion in Healthy Chinese Subjects and Population Pharmacokinetic/Pharmacodynamic Analysis to Inform Clinical Efficacy in Invasive Infections Caused by Candida albicans

Objective: This study evaluated the pharmacokinetics, safety, and bioequivalence (BE) of two formulations of rasagiline tablets in healthy Chinese subjects under fasting and fed conditions.Methods: An open, randomized, single-dose, double-cycle, two-sequence, self-crossover pharmacokinetic study in healthy Chinese subjects under fasting and high-fat postprandial conditions was performed. A total of 108 healthy subjects (36 in the fasting group and 72 in the postprandial group) were recruited. In each cycle of the study under both conditions, subjects received a single oral dose of 1 mg of a test or reference preparation of rasagiline tablets (1 mg each). A washout period of 3 days was observed. Blood samples were obtained up to 10 h post-intake. Primary endpoints were the BE of major pharmacokinetic parameters (AUC0–t and AUC0–∞) and the maximum observed serum concentration (Cmax). Secondary endpoints were safety parameters.Results: The 90% confidence interval (CI) of the geometric mean ratio (GMR) of the test drug vs. the reference drug for rasagiline was 94.16–105.35% for the AUC0–t under fasting conditions and 99.88–107.07% under postprandial conditions. The 90% CIs for the AUC0–∞ were 93.55–105.01% and 99.59–107.05% under fasting and postprandial conditions, respectively. The 90% CIs for the Cmax were 88.26–108.46% and 89.54–118.23% under fasting and postprandial conditions, respectively. The 90% CIs for the test/reference AUC ratio and Cmax ratio were within the acceptable range (0.80–1.25) for BE. In this BE study, there were no serious adverse events (AEs).Conclusion: BE between the test and the reference products was established in both fasting and postprandial conditions. The two formulations of rasagiline showed good tolerability and a similar safety profile.Clinical Trial Registration:chinaDrugtrials.org.cn, identifier CTR20181466.

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Pharmacokinetics, Safety and Tolerability of Sacubitril/Valsartan (LCZ696) After Single-Dose Administration in Healthy Chinese Subjects

European Journal of Drug Metabolism and Pharmacokinetics ◽

10.1007/s13318-016-0328-3 ◽

2016 ◽

Vol 42 (1) ◽

pp. 109-116 ◽

Cited By ~ 12

Author(s):

Yi Han ◽

Surya Ayalasomayajula ◽

Wei Pan ◽

Fan Yang ◽

Yaozong Yuan ◽

...

Keyword(s):

Single Dose ◽

Dose Administration ◽

Single Dose Administration ◽

Healthy Chinese ◽

Chinese Subjects

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

10.21203/rs.3.rs-47842/v1 ◽

2020 ◽

Author(s):

Li Xin ◽

Chenjing Wang ◽

Ting Li ◽

Yanping Liu ◽

Shuqin Liu ◽

...

Keyword(s):

Single Dose ◽

Randomized Study ◽

Pharmacokinetic Parameters ◽

Reference Formulation ◽

High Fat ◽

Fasting Condition ◽

Test Formulation ◽

Healthy Chinese ◽

Chinese Subjects ◽

Fat Meal

Abstract Background: Levamlodipine, a calcium channel blocker, is used in treatment of hypertension. 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 fasting and high-fat meal group 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 hours later. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was applied to determine levamlodipine in the plasma samples.Results: Within equivalence limits between 80 ~ 125%, the test formulation and the reference formulation were bioequivalent, with the 90% confidence intervals (CIs) for the ratio of geometric means of Cmax, AUC0-t, and AUC0-∞. The data were shown as Cmax (89.59% ~ 101.61%), AUC0-t (87.83% ~ 94.87%) and AUC0-∞ (86.28% ~ 93.49%) under fasting condition, Cmax (90.93% ~ 102.37%), AUC0–t (95.75% ~ 104.93%) and AUC0–∞ (95.36% ~ 105.33%) under high-fat meal condition. Serious adverse event was not observed.Conclusions: 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 fasting condition and high-fat meal condition.Trial registration: Cinicaltrials, NCT04411875. Registered 3 June 2020 - Retrospectively registered, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009W1Q&selectaction=Edit&uid=U00050YQ&ts=3&cx=-6iqkm8

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

10.21203/rs.3.rs-47842/v2 ◽

2020 ◽

Author(s):

Li Xin ◽

Chenjing Wang ◽

Ting Li ◽

Yanping Liu ◽

Shuqin Liu ◽

...

Keyword(s):

Single Dose ◽

Randomized Study ◽

Plasma Concentrations ◽

Bioequivalence Study ◽

Pharmacokinetic Parameters ◽

Open Label ◽

Liquid Chromatography Tandem Mass ◽

The Mean ◽

Healthy Chinese ◽

Chinese Subjects

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 hours 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, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S0009W1Q&selectaction=Edit&uid=U00050YQ&ts=3&cx=-6iqkm8

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Superior Efficacy of Liposomal Amphotericin B with Prolonged Circulation in Blood in the Treatment of Severe Candidiasis in Leukopenic Mice

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.42.9.2431 ◽

1998 ◽

Vol 42 (9) ◽

pp. 2431-2433 ◽

Cited By ~ 11

Author(s):

Els W. M. van Etten ◽

Susan V. Snijders ◽

Wim van Vianen ◽

Irma A. J. M. Bakker-Woudenberg

Keyword(s):

Body Weight ◽

Candida Albicans ◽

Single Dose ◽

Polyethylene Glycol ◽

Amphotericin B ◽

Liposomal Amphotericin ◽

Low Dose ◽

Systemic Candidiasis ◽

Superior Efficacy ◽

Single Dose Treatment

ABSTRACT In leukopenic mice with severe systemic candidiasis, single-dose treatment (5 mg of amphotericin B [AMB]/kg of body weight) with long-circulating polyethylene glycol-coated AMB liposomes (PEG-AMB-LIP) resulted in zero mortality and a significant reduction in the number of viable Candida albicans in the kidney, whereas 70% mortality was seen in mice treated with five daily doses of AmBisome (5 mg of AMB/kg · day). When the first of five daily doses of AmBisome was combined with a single low dose of Fungizone (0.1 mg of AMB/kg), the efficacy was equal to that of PEG-AMB-LIP.

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