Research Landscape of Physiologically Based Pharmacokinetic Model Utilization in Different Fields: A Bibliometric Analysis (1999-2023).

PURPOSE: The physiologically based pharmacokinetic (PBPK) modeling has received increasing attention owing to its excellent predictive abilities. However, there has been no bibliometric analysis about PBPK modeling. This research aimed to summarize the research development and hot points in PBPK model utilization overall through bibliometric analysis. METHODS: We searched for publications related to the PBPK modeling from 1999 to 2023 in the Web of Science Core Collection (WoSCC) database. The Microsoft Office Excel, CiteSpace and VOSviewers were used to perform the analyses. RESULTS: A total of 4,649 records from 1999 to 2023 were identified, and the largest number of publications focused in the period 2018-2023. The United States was the leading country, and the Environmental Protection Agency (EPA) was the leading institution. The journal Drug Metabolism and Disposition published and co-cited the most articles. Drug-drug interactions, special populations, and new drug development are the main topics in this research field. CONCLUSION: We first visualize the research landscape and hotspots of the PBPK modeling through bibliometric methods. Our study provides a better understanding for researchers, especially beginners about the dynamization of PBPK modeling and presents the relevant trend in the future.

Ocular disorders associated with PCSK9 inhibitors: A pharmacovigilance disproportionality analysis.

AIMS: To identify and characterize ocular adverse events (oAEs) that are significantly associated with proprotein convertase subtilisin-like/kexin type 9 (PCSK9) inhibitors using the US Food and Drug Administration Adverse Event Reporting System (FAERS). METHODS: We conducted a disproportionality analysis of PCSK9 inhibitors in the FAERS (01/2004-12/2021). The association between PCSK9 inhibitors and oAEs was evaluated using the information component (IC) and the reporting odds ratio (ROR), and the difference in oAEs between evolocumab and alirocumab was compared using the ROR. Different sensitivity analyses were conducted to evaluate the robustness of results. RESULTS: A total of 103 531 reports involving at least 1 PCSK9 inhibitor were found in the FAERS. PCSK9 inhibitors were associated with higher reporting of increased lacrimation (IC 0.27 [95% confidence interval {CI} 0.02-0.45]; ROR 1.21 [95% CI 1.04-1.40]), seasonal allergy (IC 0.39 [95% CI 0.04-0.64]; ROR 1.32 [95% CI 1.07-1.62]) and eye operation (IC 0.66 [95% CI 0.04-1.10]; ROR 1.60 [95% CI 1.11-2.30]) compared with the full database, and there was no difference between evolocumab and alirocumab. Sensitivity analyses showed that the disproportionate signals of increased lacrimation disappeared after excluding cases with other lipid-lowering agents in the combined drugs. Except for eye operations, most of these adverse events occurred within 30 days of the first dose, and all 3 oAEs were mostly reported in women and individuals >65 years. CONCLUSION: This pharmacovigilance study identified a possible signal of ocular disorders associated with PCSK9 inhibitors and encourages paying attention to at-risk populations in PCSK9 inhibitors medication.

Metabolic effects of the dual SGLT 1/2 inhibitor sotagliflozin on blood pressure and body weight reduction in people with diabetes: An updated meta-analysis of randomized controlled trials.

AIM: To update the meta-analysis of the metabolic effects of a dual sodium-glucose co-transpoter-1/2 inhibitor, sotagliflozin, on blood pressure (BP) and body weight in people with diabetes. METHODS: An electronic search up to March 8, 2022, were conducted to determine eligible randomized-controlled trials of sotagliflozin-reporting BP and weight change outcomes in adults with diabetes. RESULTS: 16 trials were included, with a combined cohort of 19,140 patients. Compared with placebo, sotagliflozin had a mean systolic blood pressure reduction (weighted mean differences (WMDs) -2.60 mmHg, 95 % CI: -2.90 to -2.30), mean diastolic blood pressure reduction (WMD -0.96 mmHg, 95 % CI: -1.17 to -0.75), and mean weight loss (WMD -1.88 kg, 95 % CI: -2.16 to -1.59). Metabolic effects on BP-lowering and weight loss were observed across diabetes status, duration of follow-up, and chronic kidney disease comorbidity. Meanwhile sotagliflozin presented significant effects on people with type 1 diabetes and showed a dose-response relationship for BP-lowering and weight loss. CONCLUSION: This meta-analysis enriches the evidence on the metabolic benefits, including BP-lowering and weight loss, of sotagliflozin, and provide a reasonable therapeutic option for managing diabetes with metabolic syndrome. Further studies will be required to elucidate its long-term effects and role in metabolic syndrome management. PROSPERO REGISTRATION NUMBER: CRD42022323945.