Systemic bismuth absorption and safety of the gastric mucosal protective bismuth potassium citrate, administered as granules and tablets in healthy Chinese and validation of a new, ICP-MS bismuth assay.

Objective This study aims to evaluate the bioequivalence of 2 formulations of rasagiline tablet (1mg) in Chinese healthy subjects. 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 of the two study periods under both conditions, subjects received a single oral dose of 1 mg test or a reference rasagiline (1 mg each). There was a 3-day washout period. Blood samples were obtained up to 10 hours post-intake. Several pharmacokinetic parameters were estimated based on the concentrations of rasagiline measured in plasma by means of LC-MS/MS. Results The geometric mean ratio (90% CI) of the test drug versus reference drug for rasagiline was 94.16% to 105.35% for AUC0-t under fasting conditions and 99.88% to 107.07% under postprandial conditions. The AUC0-∞s were 93.55% to 105.01% and 99.59% to 107.05% under fasting and postprandial conditions, respectively. The Cmax values were 88.26% to 108.46% and 89.54% to 118.23% under two conditions, respectively. The 90% CIs for test/reference AUC ratio and Cmax ratio were within the acceptable range (0.80–1.25) for BE. There were no serious adverse events (AEs) encountered during this BE study. Conclusion Bioequivalence between the test and the reference products was established in both fasting and postprandial conditions. The two types of rasagiline showed good tolerability and a similar safety profile.

Plasma estrogen concentrations after oral and vaginal estrogen administration in women with atrophic vaginitis

We conducted a phase I bioequivalence trial in healthy Chinese subjects in the fasting and postprandial states. The goal of this trial was to compare the pharmacokinetics and safety of the test preparation Cefaclor granule (Disha Pharmaceutical Group Co., Ltd.) and the reference preparation Cefaclor suspension (Ceclor®, Eli Lilly and Company). In this trial, 24 subjects were selected in the fasting and postprandial states, respectively. Enrolled subjects randomly accepted a single dose of 0.125 g Cefaclor granule or Cefaclor suspension. The washout period was set as 2 days. Blood samples were collected within 8 h after administration in the fasting state and within 10 h after administration in the postprandial state. Plasma concentrations were determined by Liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters (AUC, Cmax) were used to evaluate bioequivalence of the two drugs. In the fasting trial, the geometric mean ratios (90% confidence intervals CIs) for Cmax, AUC0-t, and AUC0-∞ were 93.01% (85.96%–100.63%), 97.92% (96.49%–99.38%) and 97.95% (96.52%–99.41%), respectively. The GMR (90% CIs) for Cmax, AUC0-t, and AUC0-∞ in postprandial state were 89.27% (81.97%–97.22%), 97.31% (95.98%–98.65%) and 97.31% (95.93%–98.71%), respectively. The 90% CIs of AUC and Cmax in the fasting and postprandial states were within the 80–125% bioequivalence range. Therefore, Cefaclor granule and Cefaclor suspension were bioequivalent and displayed similar safety profiles. Furthermore, food intake affected the pharmacokinetic parameters of both drugs.

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.

BackgroundOur study aims to explore the effect of genetics on the pharmacodynamics (PD) and pharmacokinetics (PK) of cinacalcet in healthy Chinese subjects; to investigate the effect of dietary factors on cinacalcet, and to evaluate the safety of cinacalcet under fasting and non-fasting conditions using a bioequivalence trial.MethodsWe investigated the relationship of cinacalcet PK with single nucleotide polymorphisms (SNPs) of CYP3A4, CYP1A2 and CYP2D6, and of cinacalcet PD with SNPs of calcium-sensitive receptors (CASR) and vitamin D receptors (VDR) in 65 healthy Chinese subjects recruited to participate in this study. Our study was a phase I, open-label, randomized, two-period, two-sequence crossover, a single-center clinical study designed under both fasting and non-fasting conditions to investigate the effect of dietary factors on cinacalcet. Plasma cinacalcet concentrations were analyzed using a validated HPLC-MS/MS assay. Clinical laboratory tests evaluated safety. Thirteen SNPs of CASR, VDR, and CYP genes were selected for pharmacogenetic analysis.ResultsCYP3A4 rs4646437 was found to be associated with the PK of cinacalcet under fasting conditions (P<0.01). Subjects carrying T alleles of rs4646437 appeared to metabolize cinacalcet poorly. The Cmax and AUC of subjects in the non-fasting group were significantly higher (P<0.0001) than those in the fasting group. The Tmax, CL/F, and Vd/F in the fasting group were significantly higher (P<0.0001) than those in the non-fasting group. In the fasting group, the geometric least square mean ratios (T/R) of the Cmax and AUC0-t were 109.89% and 105.33%, and the corresponding 90% CIs were 98.36–122.79% and 98.04–113.15%, respectively. In the non-fasting group, the T/R of the Cmax and AUC0-t were 100.74% and 99.09%, and the corresponding 90% CIs were 92.65–109.54% and 94.79–103.58%, respectively. All adverse events (AEs) were mild, and no serious adverse events (SAEs) occurred during the bioequivalence trial.ConclusionsFollowing our investigation, we reached the following conclusions: CYP3A4 rs4646437 may affect cinacalcet PK; the reference and test preparations of cinacalcet were bioequivalent under fasting and non-fasting conditions and were safe to use; and dietary factors had a significant effect on the PK of cinacalcet, in that exposure to the drug increased when cinacalcet was taken after eating.

Tegoprazan is a potassium-competitive acid blocker that inhibits gastric acid and which may be used for eradicating Helicobacter pylori. This study focuses on the pharmacokinetic interaction and safety between tegoprazan and the combination ofclarithromycin, amoxicillin and bismuth in healthy Chinese subjects. An open-label, three-period, single-center, multiple-dosage, single-sequence, phase I trial was conducted in 22 healthy subjects. In period 1, the subjects took tegoprazan 50 mg twice daily for 7 days, and in period 2 they were administered clarithromycin 500 mg, amoxicillin 1000 mg and bismuth potassium citrate 600 mg twice daily for 7 days (days 14-20). Tegoprazan, clarithromycin, amoxicillin and bismuth potassium citrate were then administered in combination for 7 days (days 21-27) in period 3. Blood samples were collected up to 12h after the last dose of each period. Safety assessments were performed in each period. The geometric mean ratios (GMRs) [90% confidence interval (CI)] of maximum plasma concentration at steady state (Cmax,ss) and area under the plasma concentration-time curve over the dosing interval (AUCτ) at steady state were 195.93% (175.52-218.71%) and 287.54% (263.28-314.04%) for tegoprazan and 423.23% (382.57-468.22%) and 385.61% (354.62-419.30%) for tegoprazan metabolite M1, respectively. The GMRs (90% CI) of Cmax,ss and AUCτ were 83.69% (77.44-90.45%) and 110.30% (102.74-118.41%) for clarithromycin, 126.25% (114.73-138.93%) and 146.94% (135.33-159.55%) for 14-hydroxyclarithromycin, 75.89% (69.73-82.60%) and 94.34% (87.94-101.20%) for amoxicillin, and 158.43% (125.43-200.11%) and 183.63% (156.42-215.58%) for bismuth, respectively. All reported adverse events were mild. The frequency of adverse events during the coadministration stage was not higher than that during the single- or triple-drug administration stages. The plasma exposure of tegoprazan, M1, 14-hydroxyclarithromycin and bismuth was increased after the coadministration of tegoprazan, clarithromycin, amoxicillin and bismuth. The coadministration exhibited favorable safety and tolerability. CTR20230643.

Objectives: (R)-ketamine hydrochloride injection is a novel, rapid-acting antidepressant for the treatment of treatment-resistant depression. The aim of this study was to assess the pharmacokinetics, safety, and tolerability of (R)-ketamine hydrochloride injection in healthy Chinese subjects following ascending single intravenous doses ranging from 10.0 mg to 180 mg. Methods: This randomized, double-blind, placebo-controlled study was conducted in 50 healthy male and female Chinese subjects after single ascending doses of (R)-ketamine hydrochloride injection (10.0, 30.0, 60.0, 120, and 180 mg). Ten subjects (including two subjects treated with a placebo) were included in each dose cohort. Pharmacokinetic characteristics, safety, and tolerability profiles of the study drug were evaluated. Results: After the intravenous doses administered from 10.0 mg to 180 mg of (R)-ketamine hydrochloride injection to the subjects, the Cmax and AUC values for both (R)-ketamine and its metabolite (R)-norketamine in the subjects increased approximately proportionally to the doses. The average peak plasma concentration levels at the five dose cohorts ranged from 56.0 to 1424 ng/mL and 27.7 to 491 ng/mL for (R)-ketamine and (R)-norketamine, respectively. The adverse events of (R)-ketamine hydrochloride injection were temporary and recovered spontaneously without treatment. Conclusions: In summary, (R)-ketamine hydrochloride injection was safe and well tolerated in healthy Chinese subjects. The clinical study results laid a foundation for the further clinical studies of (R)-ketamine hydrochloride injection in patients.

The single-pill combination of rosuvastatin and ezetimibe effectively reduces low-density lipoprotein cholesterol (LDL-C), while the pharmacokinetics of the single-pill combination of rosuvastatin and ezetimibe at a dosage of 2.5mg/10mg are seldom reported. This study aimed to evaluate the pharmacokinetics of a single-pill combination of rosuvastatin and ezetimibe (2.5mg/10mg) in healthy Chinese adult subjects. In this open-label, two-period, phase I study, 16 healthy subjects were enrolled and were administered a single-pill combination of rosuvastatin and ezetimibe (2.5mg/10mg) on day (D) 1 (single-dose period) and D14 to D23 once daily (multiple-dose period) under fasting conditions. The plasma concentrations of free ezetimibe, total ezetimibe, and rosuvastatin were determined. The pharmacokinetic parameters, including peak plasma concentration (Cmax), area under the curve from zero to last measurement (AUC0-t), and area under the curve from zero to infinity (AUC0-∞), were subsequently calculated. During the single-dose period, the Cmax, AUC0-t, and AUC0-∞ were 4.7 ± 2.8ng/mL, 99.6 ± 40.7h*ng/mL, and 97.1 ± 35.9h*ng/mL for free ezetimibe; 59.5 ± 27.6ng/mL, 564.7 ± 177.3h*ng/mL, and 580.5 ± 190.1h*ng/mL for total ezetimibe; and 2.7 ± 1.3ng/mL, 21.8 ± 11.3h*ng/mL, and 23.1 ± 11.5h*ng/mL for rosuvastatin, respectively. During the multiple-dose period, the C was 9.0 ± 4.6ng/mL for free ezetimibe, 77.0 ± 30.1ng/mL for total ezetimibe, and 3.1 ± 1.1ng/mL for rosuvastatin. LDL-C reached a reduction of 37.7 ± 9.0%, 44.4 ± 8.3%, and 16.0 ± 16.3% at D20, D23, and D28, respectively, compared with its level at D13 (all P < 0.05). The total adverse event (AE) rate was 81.3%, and all these AEs were Grade I. The single-pill combination of rosuvastatin and ezetimibe (2.5mg/10mg) indicates a steady pharmacokinetic characteristic, a good lipid-lowering effect, and a safe profile in healthy Chinese subjects.

This study aimed to assess the bioequivalence and safety of two formulations of sorafenib in healthy Chinese subjects under fasting conditions. A single-center, randomized, open, single-dose, two-formulation, four-period, crossover study was performed in 36 healthy Chinese subjects under fasting conditions. Blood samples were collected within 120h after administration. The plasma concentrations of sorafenib were analyzed by a validated UPLC-MS/MS method, and pharmacokinetic parameters were analyzed using a non-compartmental method. Safety was assessed on the basis of the occurrence of adverse events and laboratory findings throughout the study period. The GMR point estimators of Cmax, AUC0-t, and AUC0-∞ for the two formulations were 88.97%, 81.67%, and 83.66%, respectively, which were within the bioequivalence criterion range of 80%-125%. The upper limits of the one-sided 95% confidence intervals of Cmax, AUC0-t, and AUC0-∞ after logarithmic transformation were -0.05, -0.04 and -0.03, respectively, which were less than 0. The difference in Tmax between these two formulations was not statistically significant according to the Wilcoxon signed-rank test (P = 0.3650 > 0.05). Therefore, the bioequivalence between the two formulations was established under fasting conditions. All adverse events were mild and transient. The T formulation was bioequivalent and showed a similar safety profile to the R formulation Nexavar® (Bayer AG) in healthy Chinese subjects under fasting conditions. http://www.chinadrugtrials.org.cn/index.html, Identifier CTR20233578.

This study evaluated the pharmacokinetic and safety profiles of generic and original blonanserin tablets under fasting and postprandial conditions, and the bioequivalence of two formulations to obtain sufficient evidence for abbreviated new drug application. A randomized, open-label, two-period, two-sequence, self-crossover bioequivalence study was conducted to assess the bioequivalence of the test and reference blonanserin tablets under fasting and postprandial conditions. Eligible healthy individuals received a single 4-mg dose of either the test or reference blonanserin tablet, followed by a wash out period of 14days. Serial blood samples were collected for up to 72h after administration during each period, and the plasma concentrations of blonanserin were determined using a validated method. The non-compartmental method was used to calculate the primary pharmacokinetic parameters, and the geometric mean ratios for the PK parameters of the test drug to those of the reference drug, along with the corresponding 90% confidence intervals, were obtained for bioequivalence analysis. Throughout the study, a safety evaluation was conducted. Under both fasting and postprandial conditions, the pharmacokinetic parameters of the test drug were found to be similar to those of the reference drug. The 90% confidence intervals (CIs) of the geometric mean ratios of the test to reference formulations were 97.79%-118.28% for peak concentration (Cmax), 92.35%-111.78% for the area under the curve from zero to the last measurable concentration (AUC0-t) and 92.88%-111.91% for the AUC from zero to observed infinity (AUC0-∞) under fasting conditions, 88.65%-103.20% for Cmax, 95.89%-106.81% for AUC0-t and 96.02%-106.91% for AUC0-∞ under postprandial conditions, all of which were within the accepted bioequivalence range of 80.00%-125.00%. Both the test and reference formulations were well-tolerated, and no serious adverse events related to the study drug were reported during the study. The bioequivalence of blonanserin tablets, both test and reference, was confirmed in healthy Chinese subjects under fasting and postprandial conditions, meeting the predetermined regulatory criteria for both formulations. Both formulations were found to be safe and well tolerated. http://www.chinadrugtrials.org.cn/index.html, identifier CTR20230703.

BackgroundCloperastine is a pivotal antibechic widely prescribed to treat cough caused by respiratory diseases. The present trial evaluated the pharmacokinetics (PK), bioequivalence (BE) and safety effects of the generic test (T) tablet of cloperastine after single-dose administration of cloperastine, compared with the original reference (R) tablet of cloperastine.ObjectiveThe purpose of this trial was to compare the PK, BE and safety of a test 10 mg versus the reference 10 mg formulation of cloperastine under fasting and postprandial conditions in healthy Chinese volunteers.MethodsA single-centre, randomised, open, double-cycle, self-crossover, single oral administration Phase I trial was performed in healthy Chinese volunteers. A total of 60 subjects were enrolled in either the fasting (28 subjects) or the postprandial condition (32 subjects). Subjects randomly received a single dose of the T or R preparation (10 mg dose). Plasma concentrations of cloperastine were analysed by a validated LC-MS/MS method. The primary endpoints of the PK parameters were the area under the plasma concentration-time curve from zero to 72 h (AUC0–72h), under the plasma concentration-time curve from zero to infinity (AUC0–∞) and the maximal plasma concentration (Cmax). The equivalence standard range (80.0–125.0%) was used to evaluate the BE of the two preparations. The safety parameter as secondary endpoint was mainly evaluated by the occurrence of adverse events (AEs).ResultsA total of 25 and 30 subjects in the fasting and postprandial conditions completed this clinical trial, respectively. The geometric mean ratio (GMR) of the T/R for the Cmax, AUC0–72h and AUC0–∞ were 102.1%, 103.8% and 104.0% in the fasting condition, respectively. In the postprandial condition, the GMR of the T/R for the Cmax, AUC0–72h and AUC0–∞ were 94.2%, 98.8% and 99.0%, respectively. All the values fell within the range (80.0–125.0%). The Cmax and AUC0–72h values of the T and R preparations in fasting and postprandial conditions were not statistically significant (P > 0.05). Furthermore, no serious adverse events (SAEs) occurred during the whole trial.ConclusionsThe T and R preparations were bioequivalent under both conditions. Food has no significant effect on the absorption of cloperastine. Moreover, T and R preparations were well tolerated. The trial registration number (TRN) and date of registrations were CTR20212515, 13 October 2021.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40268-022-00406-2.

ObjectivesThis study assessed the pharmacokinetics, safety, and bioequivalence of generic and original palbociclib tablets in healthy Chinese subjects under fasting conditions with rabeprazole pre-treatment.MethodsThis was a single-dose, randomized, open-label, two-period crossover bioequivalence study conducted under fasting conditions with rabeprazole pre-treatment. In each trial, healthy Chinese subjects received 40 mg oral rabeprazole enteric-coated tablets once daily before breakfast for 6 days. Following an overnight fast of at least 10 h, they took the seventh dose of rabeprazole and maintained fasting. They then received a single 125 mg oral dose of either the test or reference palbociclib tablet, followed by a 14-day washout interval between periods. Blood samples were collected from 0 to 96 h post-dose in each period, and palbociclib plasma concentrations were determined using a validated method. The primary pharmacokinetic parameters were calculated using the non-compartmental method. The geometric mean ratios of the two formulations and the corresponding 90% confidence intervals were acquired for bioequivalence analysis. The safety of both formulations was also evaluated.ResultsThe 90% confidence intervals for the primary pharmacokinetic parameters of Cmax (84.53%–91.72%), AUC0-t (87.81%–92.49%), and (87.59%–92.03%) all fell within the 80.00%–125.00% bioequivalence range. No serious adverse events occurred during the study.ConclusionThe trial confirmed that the pharmacokinetic parameters of the generic and original palbociclib tablets were bioequivalent in healthy Chinese subjects under fasting conditions with rabeprazole pre-treatment. Both formulations were safe and well tolerated.Clinical Trial Registrationhttp://www.chinadrugtrials.org.cn, identifier CTR20232617; https://www.chictr.org.cn, identifier ChiCTR2400084355.

D-1553 (garsorasib) is a novel and selective oral KRASG12C inhibitor. This study aims to evaluate the effect of food on the single-dose pharmacokinetics (PK) of D-1553 tablet in healthy Chinese subjects. Also the safety and tolerability of single-dose D-1553 in subjects are also evaluated. A randomized, open-label, single-dose, two-intervention (fed vs fasting), two-period, two-sequence crossover study was performed on 14 healthy Chinese subjects. Plasma concentrations of D-1553 were determined by the liquid chromatography-tandem mass spectrometry method. Safety evaluations were carried out during the study period. The main PK parameters of the two formulations of D-1553 were calculated by non-compartmental analysis using Phoenix WinNonlin (Version 8.3) software. The geometric mean ratios (90% confidence interval [CI]) of AUC0-t and AUC0-∞ in the high-fat meal condition versus the fasting condition were 86.19% (78.30%, 94.87%) and 83.30% (75.77%, 91.58%), respectively. The geometric mean ratio (90% CI) of Cmax values in high-fat meal condition to that observed in fasting condition were 109.74% (100.22%,120.15%). The p value of Tmax was 0.1484 (fed vs fasting). Two subjects (14.3%) reported 4 treatment-emergent adverse events (TEAEs) in the fasting condition, and no subjects reported TEAEs in the fed condition. All adverse reactions were mild and had recovered by the end of the study. The study indicated that a high-calorie and high-fat meal has no clinically relevant impact on the PK and bioavailability of D-1553 in healthy Chinese subjects. D-1553 was generally safe and well-tolerated under both fasting and fed conditions. The findings suggest that D-1553 could be administered orally with or without food. ClinicalTrials.gov Identifer CTR20212761; registered on 4 Nov 2021.

Introduction Reactive oxygen species, potentially formed through environmental or lifestyle exposures, can overwhelm an organism’s antioxidant capabilities resulting in oxidative stress. Long-term oxidative stress is linked with chronic diseases including breast, prostate, and lung cancers. We utilised a longitudinal study of corn farmers and non-farming controls in Iowa to examine the impact of exposure to atrazine and 2,4-dichlorophenoxyacetic acid (2,4-D) on markers of oxidative stress. These pesticides are associated with oxidative stress in vivo, as well as cancer, and are among the most widely used herbicides in the United States. Methods The study included 225 urine samples collected through the growing season (pre-planting, planting, growing season, harvest, and off-season) of 10 controls who did not apply pesticides occupationally and 30 farmers who did; all were non-smoking men ages 40 to 60 years. Atrazine mercapturate (an atrazine metabolite), 2,4-D, and oxidative stress markers (malondialdehyde [MDA], 8-hydroxy-2′-deoxyguanosine [8-OHdG], and 8-„isoprostaglandin-F2α [8-isoPGF]) were measured in urine samples. We calculated β estimates and p-values for each pesticide-oxidative stress marker combination using linear mixed-effect models adjusted for creatinine, time, and other covariates in order understand the impact of exposure to these herbicides on oxidative stress. Results Overall, farmers had higher urinary atrazine mercapturate and 2,4-D levels compared to controls. In multivariate linear mixed-effect regression models, after natural log transformation, 2,4-D was associated with elevated levels of 8-OHdG (β = 0.047, p = 0.048) and 8-isoPGF (β = 0.076, p = 0.075). We saw no associations with 2,4-D and MDA. Atrazine mercapturate was not associated with any of the oxidative stress markers. Discussion Our data suggest 2,4-D exposure may be associated with oxidative stress because of increases of 8-OHdG, a marker of oxidative DNA damage, and 8-isoPGF, a product of lipoprotein peroxidation with exposure. Future studies should attempt to understand the role of 2,4-D-induced oxidative stress in the pathogenesis of human disease, particularly cancer.

BackgroundPotassium bismuth citrate is a gastric mucosal protector and a key drug for treating peptic ulcers.ObjectiveTo evaluate the pharmacokinetic characteristics and safety of 120-mg bismuth potassium citrate formulations administered orally under fasting conditions in healthy Chinese subjects.MethodA single-center open two-cycle trial was conducted on 12 healthy subjects who received a single oral dose of 120 mg of bismuth potassium citrate. The plasma concentration of bismuth was determined using a validated inductively coupled plasma mass spectrometry (ICP‒MS) method. The pharmacokinetic parameters, including maximum serum concentration (Cmax) and area under the curve concentration–time curve (AUC0–t and AUC0–∞), and safety were evaluated via noncompartment analysis.ResultsThe ratios of the least square geometric mean ratio between the test (T) and reference (R) formulations for Cmax, AUC0–t, and AUC0–∞ were 44.8%, 55.5%, and 64.4%, respectively; the bilateral 95% confidence intervals (Cis) for these parameters were 20.2–99.6%, 24.1–127.5%, and 23.7–175.0%, respectively, and the non-inferior limits for these parameters were 169.4%, 198.8%, and 200.5%, respectively. The upper limits of the one-sided 97.5% confidence interval for the least squares geometric mean ratio (T/R) were lower than the non-inferior limits. No serious adverse reactions or adverse reactions leading to detachment were observed among the subjects.ConclusionThe concentration of bismuth in the blood of healthy subjects in the T formulation was not greater than that in the R formulation. Similarly, the safety of oral administration of 120 mg of bismuth potassium citrate formulations to healthy subjects was good. The trial registration number (TRN) was [2018] 013, 6 December 2018.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40268-024-00455-9.