Pharmacokinetics of Liposomal Amphotericin B for Injection in Chinese Healthy Subjects Based on a Bioequivalence Study

ABSTRACT The pharmacokinetics, excretion, and mass balance of liposomal amphotericin B (AmBisome) (liposomal AMB) and the conventional formulation, AMB deoxycholate (AMB-DOC), were compared in a phase IV, open-label, parallel study in healthy volunteers. After a single 2-h infusion of 2 mg of liposomal AMB/kg of body weight or 0.6 mg of AMB-DOC/kg, plasma, urine, and feces were collected for 168 h. The concentrations of AMB were determined by liquid chromatography tandem mass spectrometry (plasma, urine, feces) or high-performance liquid chromatography (HPLC) (plasma). Infusion-related side effects similar to those reported in patients, including nausea and back pain, were observed in both groups. Both formulations had triphasic plasma profiles with long terminal half-lives (liposomal AMB, 152 ± 116 h; AMB-DOC, 127 ± 30 h), but plasma concentrations were higher (P < 0.01) after administration of liposomal AMB (maximum concentration of drug in serum [C max], 22.9 ± 10 μg/ml) than those of AMB-DOC (C max, 1.4 ± 0.2 μg/ml). Liposomal AMB had a central compartment volume close to that of plasma (50 ± 19 ml/kg) and a volume of distribution at steady state (V ss) (774 ± 550 ml/kg) smaller than the V ss of AMB-DOC (1,807 ± 239 ml/kg) (P < 0.01). Total clearances were similar (approximately 10 ml hr−1 kg−1), but renal and fecal clearances of liposomal AMB were 10-fold lower than those of AMB-DOC (P < 0.01). Two-thirds of the AMB-DOC was excreted unchanged in the urine (20.6%) and feces (42.5%) with >90% accounted for in mass balance calculations at 1 week, suggesting that metabolism plays at most a minor role in AMB elimination. In contrast, <10% of the liposomal AMB was excreted unchanged. No metabolites were observed by HPLC or mass spectrometry. In comparison to AMB-DOC, liposomal AMB produced higher plasma exposures and lower volumes of distribution and markedly decreased the excretion of unchanged drug in urine and feces. Thus, liposomal AMB significantly alters the excretion and mass balance of AMB. The ability of liposomes to sequester drugs in circulating liposomes and within deep tissue compartments may account for these differences.

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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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Randomized, Open-Label, Two-Way Crossover Study To Compare The Bioequivalence Of Two Formulations Of Esomeprazole In Healthy Male Volunteers

KYAMC Journal ◽

10.3329/kyamcj.v4i1.32254 ◽

2017 ◽

Vol 4 (1) ◽

pp. 326-330

Author(s):

Uttam Kumar Sarker ◽

Mir Misbahuddin ◽

Md Shariful Hasan Ripon ◽

Md Rabiul Islam

Keyword(s):

Half Life ◽

Plasma Concentrations ◽

Bioequivalence Study ◽

Relative Bioavailability ◽

Hplc Method ◽

Pharmacokinetic Parameters ◽

Test Drug ◽

Healthy Male ◽

Open Label ◽

Reference Drug

A crossover-randomized bioequivalence study of two oral formulations of esomeprazole (40 mg) capsules were carried out in 16 healthy male Bangladeshi volunteers. The test and reference formulations were PRONEX (Drug International Ltd, Bangladesh) and NEXIUM (AstraZeneca AB, Sweden), respectively. Each tablet was administered with 150 mL of water to subjects after overnight fasting on 2 treatment days separated by 1 week washout period. After dosing, serial blood samples were collected for a period of 24 hours. The plasma concentrations of esomeprazole were estimated using a validated HPLC method. The pharmacokinetic parameters Cmax, Tmax, AUC0g24h, t1/2, and Kel were determined. The mean (± SD) AUC0g24h for esomeprazole of test drug PRONEXTM for 16 volunteers was 1509 (± 546) ng.hr/mL whereas it was 1622 (± 589) ng.hr/mL for esomeprazole of NEXIUMTM. The relative bioavailability (PRONEXTM/NEXIUMTM ratio) was 93%. The Cmax, tmax, half-life of elimination (t1/2) and the rate of elimination (Kel) of esomeprazole of test drug were 1653 (± 706) ng/mL, 2.13 (± 0.81) hours, 2.00 (± 0.61) hour and 0.3465 respectively. The Cmax, tmax, half-life of elimination (t1/2) and the rate of elimination (Kel) of esomeprazole of reference drug were 1820 (± 877) ng/mL, 2.80 (± 0.67) hours, 2.14 (± 0.55) hour and 0.3238 respectively. The 90% CI for the test and reference drugs were found within the acceptance range of 80-125%. In conclusion, PRONEX is bioequivalent to NEXIUM in terms of absorption.KYAMC Journal Vol. 4, No.-1, July 2013, Page 326-330

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Combination of topical liposomal amphotericin B and Glucantime in comparison with glucantime alone for the treatment of anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica: study protocol for a randomized, controlled trial

Iranian Journal of Microbiology ◽

10.18502/ijm.v13i5.7440 ◽

2021 ◽

Author(s):

Seyed Ebrahim Eskandari ◽

Ali Khamesipour ◽

Mahmoud Reza Jaafari ◽

Amir Javadi ◽

Akram Miramin Mohammadi ◽

...

Keyword(s):

Cutaneous Leishmaniasis ◽

Amphotericin B ◽

Liposomal Amphotericin ◽

Controlled Trial ◽

Liposomal Amphotericin B ◽

Topical Formulation ◽

Liposomal Form ◽

Double Blind ◽

Well Design ◽

Intralesional Injections

Background and Objectives: Cutaneous leishmaniasis (CL) treatment is a challenging issue, although numerous modalities have been introduced as candidate treatment for CL yet only antimonial agents are commonly used to treat CL, a different form of amphotericin B is used to treat visceral form of leishmaniasis but the efficacy against CL is not high. There are a few reliable clinical trials on CL, the main reason is the nature of the disease which required a well design protocol to evaluate the efficacy of any candidate treatment against CL. In this study, a protocol was developed and used to evaluate a topical formulation of a nano-liposomal form of amphotericin B in addition to glucantime to treat CL caused by L. tropica. Materials and Methods: This study is a phase 3, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of topical nano-liposomal amphotericin B (SinaAmpholeish 0.4%) in combination with intralesional injections of meglumine antimoniate in the treatment of ACL caused by L. tropica. Overall, 130 patients, aged 12-60 years, with a diag- nosis of ACL caused by L. tropica are recruited and treated according to the protocol. Results: A total of 130 patients with CL lesion will be recruited and double- blind randomly treated with received intralesional injections of Glucantime weekly or Glucantime plus SinaAmpholeish for 4 weeks. Conclusion: The results of this study showed that the protocol works well and the treatment was tolerated by both groups of patients.

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Pharmacokinetic Characterisation and Comparison of Bioavailability of Intranasal Fentanyl, Transmucosal, and Intravenous Administration through a Three-Way Crossover Study in 24 Healthy Volunteers

Pain Research and Management ◽

10.1155/2021/2887773 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

S. Nardi-Hiebl ◽

J. W. Ndieyira ◽

Y. Al Enzi ◽

W. Al Akkad ◽

T. Koch ◽

...

Keyword(s):

Healthy Volunteers ◽

Intravenous Administration ◽

Intranasal Administration ◽

Geometric Mean ◽

Plasma Concentrations ◽

Pharmacokinetic Parameters ◽

Published Data ◽

Open Label ◽

Single Dose Study ◽

Transmucosal Administration

Background. For more than 60 years, the synthetic opioid fentanyl has been widely used in anaesthesia and analgesia. While the intravenous formulation is primarily used for general anaesthesia and intensive care settings, the drug’s high lipophilic properties also allow various noninvasive routes of administration. Published data suggest that intranasal administration is also attractive for use as intranasal patient-controlled analgesia (PCA). A newly developed intranasal fentanyl formulation containing 47 μg fentanyl, intravenous fentanyl, and oral transmucosal fentanyl citrate were characterised, and bioavailability was compared to assess the suitability of the intranasal formulation for an intranasal PCA product. Methods. 27 healthy volunteers were enrolled in a single-centre, open-label, randomised (order of treatments), single-dose study in a three-period crossover design. The pharmacokinetics of one intranasal puff of fentanyl formulation (47 μg, 140 mL per puff), one short intravenous infusion of 50 μg fentanyl, and one lozenge with an integrated applicator (200 μg fentanyl) were studied, and bioavailability was calculated. Blood samples were collected over 12 hours, and plasma concentrations of fentanyl were determined by HPLC with MS/MS detection. Results. 24 volunteers completed the study. The geometric mean of AUC0-tlast was the highest with oral transmucosal administration (1106 h ∗ pg/ml, CV% = 32.86), followed by intravenous (672 h ∗ pg/ml, CV% = 32.18) and intranasal administration (515 h ∗ pg/ml, CV% = 30.10). Cmax was 886 pg/ml (CV% = 59.38) for intravenous, 338 pg/ml (CV% = 45.61) for intranasal, and 310 pg/ml (CV% = 29.58) for oral transmucosal administration. tmax was shortest for intravenous administration (0.06 h, SD = 0.056), followed by intranasal (0.21 h, SD = 0.078) and oral transmucosal administration (1.20 h, SD = 0.763). Dose-adjusted relative bioavailability was determined to be 74.70% for the intranasal formulation and 41.25% for the oral transmucosal product. In total, 38 adverse events (AEs) occurred. Fourteen AEs were potentially related to the investigational items. No serious AE occurred. Conclusion. Pharmacokinetic parameters and bioavailability of the investigated intranasal fentanyl indicated suitability for its intended use as an intranasal PCA option.

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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/v3 ◽

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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A comparative study of plasma concentrations of liposomal amphotericin B (L-AMP-LRC-1) in adults, children and neonates

International Journal of Pharmaceutics ◽

10.1016/s0378-5173(02)00066-2 ◽

2002 ◽

Vol 238 (1-2) ◽

pp. 11-15 ◽

Cited By ~ 22

Author(s):

Rajshree N. Kotwani ◽

Prafulla C. Gokhale ◽

Prashant V. Bodhe ◽

Babita G. Kirodian ◽

Nilima A. Kshirsagar ◽

...

Keyword(s):

Comparative Study ◽

Amphotericin B ◽

Liposomal Amphotericin ◽

Plasma Concentrations ◽

Liposomal Amphotericin B

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

BMC Pharmacology and Toxicology ◽

10.1186/s40360-020-00459-6 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Xin Li ◽

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 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

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Evaluation of tramadol human pharmacokinetics and safety after co-administration of magnesium ions in randomized, single- and multiple-dose studies

Pharmacological Reports ◽

10.1007/s43440-021-00239-x ◽

2021 ◽

Vol 73 (2) ◽

pp. 604-614

Author(s):

Piotr J. Rudzki ◽

Katarzyna Jarus-Dziedzic ◽

Monika Filist ◽

Edyta Gilant ◽

Katarzyna Buś-Kwaśnik ◽

...

Keyword(s):

Confidence Intervals ◽

Multiple Dose ◽

Geometric Mean ◽

Plasma Concentrations ◽

Pharmacokinetic Parameters ◽

Human Pharmacokinetics ◽

Magnesium Ions ◽

Open Label ◽

Multiple Dose Study ◽

Dose Study

Abstract Background Magnesium ions (Mg2+) increase and prolong opioid analgesia in chronic and acute pain. The nature of this synergistic analgesic interaction has not yet been explained. Our aim was to investigate whether Mg2+ alter tramadol pharmacokinetics. Our secondary goal was to assess the safety of the combination. Methods Tramadol was administered to healthy Caucasian subjects with and without Mg2+ as (1) single 100-mg and (2) multiple 50-mg oral doses. Mg2+ was administered orally at doses of 150 mg and 75 mg per tramadol dosing in a single- and multiple-dose study, respectively. Both studies were randomized, open label, laboratory-blinded, two-period, two-treatment, crossover trials. The plasma concentrations of tramadol and its active metabolite, O-desmethyltramadol, were measured. Results A total of 25 and 26 subjects completed the single- and multiple-dose study, respectively. Both primary and secondary pharmacokinetic parameters were similar. The 90% confidence intervals for Cmax and AUC0-t geometric mean ratios for tramadol were 91.95–102.40% and 93.22–102.76%. The 90% confidence intervals for Cmax,ss and AUC0-τ geometric mean ratios for tramadol were 93.85–103.31% and 99.04–105.27%. The 90% confidence intervals for primary pharmacokinetic parameters were within the acceptance range. ANOVA did not show any statistically significant contribution of the formulation factor (p > 0.05) in either study. Adverse events and clinical safety were similar in the presence and absence of Mg2+. Conclusions The absence of Mg2+ interaction with tramadol pharmacokinetics and safety suggests that this combination may be used in the clinical practice for the pharmacotherapy of pain. Graphic abstract

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Effect of high-fat diet on the pharmacokinetics and safety of flumatinib in healthy Chinese subjects

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-020-04117-w ◽

2020 ◽

Vol 86 (3) ◽

pp. 339-346

Author(s):

Yun Kuang ◽

Hui-ling Song ◽

Guo-ping Yang ◽

Qi Pei ◽

Xiao-yan Yang ◽

...

Keyword(s):

High Fat Diet ◽

Geometric Mean ◽

Plasma Concentrations ◽

Least Square ◽

Pharmacokinetic Parameters ◽

High Fat ◽

Open Label ◽

Clinical Trial Registration ◽

Healthy Chinese ◽

Chinese Subjects

Abstract Purpose To evaluate the effect of a high-fat diet on the pharmacokinetics and safety of flumatinib mesylate tablets in healthy Chinese subjects. Methods This study was a randomized, open-label, single-dose, two-period crossover trial in which subjects were randomly assigned to take 400 mg of flumatinib mesylate after a high-fat diet or a fasted state. After a 14-day washout period, the two groups were administered flumatinib mesylate under opposite conditions. Blood samples were collected at baseline 0 and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 48, 72, and 96 h, respectively. Plasma concentrations of flumatinib and its metabolites (M1 and M3) were analyzed using liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated using the non-compartmental module of the Phoenix WinNonlin Version 7.0 software. BE module of WinNonLin was used for statistical analysis of AUC0–t, AUC0–∞ and Cmax in plasma. Results Twelve healthy subjects, half male and half female, were enrolled. One subject withdrew due to a treatment-emergent adverse event. Eleven subjects were administered drugs on fasting and 12 were administered drugs after a high-fat diet. On high-fat diet/fasting, the least square geometric mean (LSGM) ratios of flumatinib, M1, M3, and their 90% confidence interval (CI) were as follows: for flumatinib, Cmax, AUC0–t and AUC0–∞ were 281.65% (225.80–351.31%), 167.43% (143.92–194.79%), and 166.87% (143.47–194.09%); for M1, Cmax, AUC0–t, and AUC0–∞ were 188.59% (145.29–244.79), 163.94% (149.11–180.24%), and 164.48% (150.36–179.94%); for M3, Cmax, AUC0–t, and AUC0–∞ were 63.47% (54.02–74.57%), 85.23% (74.72–97.22%), and 96.73% (86.63–108.02%). Conclusion Among the subjects, oral administration of 400 mg of flumatinib was safe and well tolerated. High-fat diet significantly increases the exposure to flumatinib, therefore, fasting may be recommended. Clinical trial registration The study was registered at chictr.org Identifier: ChiCTR-IIR-17013179.

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