An analysis of the biopharmaceutical behaviour of proton pump inhibitors with different physicochemical properties

Jiang, Xin‐Dong; Shen, Tianxiang; Zhong, Jun; Li, Chunlong; Li, Qingpo; Qiu, Weigen; Cui, Yannan; Han, Zheng‐Fu; Hou, Xuemei; You, Jian

doi:10.1016/j.lfs.2021.120042

Cited by 2 publications

(2 citation statements)

References 15 publications

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“…Similar to other PPI drugs, anaprazole primarily localizes in the digestive tract, particularly the stomach and small intestine, following oral administration, which is its pharmacologically active site 18 . In this study, we found that the median t max of anaprazole was 3‐5.25 hours with mean t 1/2z value of 1.22‐3.79 hours in healthy Chinese subjects after single‐dose (5‐120 mg) or multiple‐dose (20 mg once‐daily, 40 mg once‐daily, or 20 mg twice‐daily) oral administration of the anaprazole sodium enteric‐coated tablet.…”

Section: Discussionmentioning

confidence: 99%

Safety, Tolerability, and Pharmacokinetics of Anaprazole, a Novel Proton Pump Inhibitor, in Healthy Chinese Subjects

Wang,

Niu,

Liu

et al. 2024

Clinical Pharm in Drug Dev

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Anaprazole, a newly developed oral proton pump inhibitor, was evaluated for safety, tolerability, and pharmacokinetics in healthy Chinese subjects. This study involved administering either anaprazole sodium enteric‐coated tablet or placebo, followed by monitoring the incidence and severity of any adverse events (AEs). The pharmacokinetic parameters of anaprazole, its isomer, and main metabolisms were determined. The results showed that both single‐dose (2.5‐120 mg) and multiple‐dose (20 mg once daily, 40 mg once daily, or 20 mg twice daily) oral administration of anaprazole sodium enteric‐coated tablet were safe and well tolerated. Following single‐dose administration, the median time to reach maximum plasma concentration of anaprazole was between 3.50 and 5.25 hours, with mean elimination half‐life of 1.22‐3.79 hours. The absorption and elimination of anaprazole in the human body appeared to basically follow linear kinetics. After repeated dosing, steady‐state concentrations of anaprazole, its isomer, and primary metabolites were achieved, with a median time to reach maximum plasma concentration of 3‐3.75 hours and a mean elimination half‐life of 1.61‐2.27 hours for anaprazole. There was no significant drug accumulation after multiple‐dose oral administration. In conclusion, anaprazole sodium enteric‐coated tablets were found to be safe and well tolerated in healthy Chinese individuals. Anaprazole is absorbed and metabolized consistently in the human body without any accumulation.

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Section: Discussionmentioning

confidence: 99%

Safety, Tolerability, and Pharmacokinetics of Anaprazole, a Novel Proton Pump Inhibitor, in Healthy Chinese Subjects

Wang,

Niu,

Liu

et al. 2024

Clinical Pharm in Drug Dev

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“…Ilaprazole is more lipophilic (LogP = 3.04) compared to other PPIs, with high plasma protein binding capacity of more than 97%. Biodistribution study after intravenous injection of 14 C-ilaprazole in rats demonstrated that it distributed in most tissues/organs and the radioactive signal of ilaprazole can still be observed in the stomach after 24 h ( Shen et al, 2020 ; Jiang et al, 2021 ). In this study, analysis of covariates indicated that the peripheral volume of distribution of ilaprazole increased with increasing body weight, which is consistent with the finding in previous studies that the volume of distribution of lipophilic drugs tends to correlate with total body weight ( Hanley et al, 2010 ; Morrish et al, 2011 ).…”

Section: Disscussionmentioning

confidence: 99%

Population pharmacokinetic modeling of ilaprazole in healthy subjects and patients with duodenal ulcer in China

Yu,

Liu,

et al. 2024

Front. Pharmacol.

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Aims: This study aimed to develop a population pharmacokinetic (PopPK) model of ilaprazole in healthy subjects and patients with duodenal ulcer in Chinese and investigate the effect of potential covariates on pharmacokinetic (PK) parameters.Methods: Pharmacokinetic data from 4 phase I clinical trials and 1 phase IIa clinical trial of ilaprazole were included in PopPK analysis. Phoenix NLME 8.3 was used to establish a PopPK model and quantify the effects of covariate, such as demographic data, biochemical indicators and disease state on the PK parameters of ilaprazole. The final model was evaluated by goodness-of-fit plots, bootstrap analysis, and visual predictive check.Results: A two-compartment model with first-order elimination successfully described the pharmacokinetic properties of ilaprazole. In the final PopPK model, body weight and sex were identified as statistically significant covariates for volume of peripheral compartment (Vp) and clearance of central compartment (CL), respectively, and disease status was also screened as a significant covariate affecting both CL and Vp. The validation results demonstrated the good predictability of the model, which was accurate and reliable.Conclusion: This is the first population pharmacokinetics study of ilaprazole in the Chinese, and the PopPK model developed in this study is expected to be helpful in providing relevant PK parameters and covariates information for further studies of ilaprazole.

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An analysis of the biopharmaceutical behaviour of proton pump inhibitors with different physicochemical properties

Cited by 2 publications

References 15 publications

Safety, Tolerability, and Pharmacokinetics of Anaprazole, a Novel Proton Pump Inhibitor, in Healthy Chinese Subjects

Safety, Tolerability, and Pharmacokinetics of Anaprazole, a Novel Proton Pump Inhibitor, in Healthy Chinese Subjects

Population pharmacokinetic modeling of ilaprazole in healthy subjects and patients with duodenal ulcer in China

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