{"title":"Notes on the Use of Kirchhoff's Laws in Pharmacokinetics.","authors":"Ronald A Siegel","doi":"10.1208/s12248-023-00875-6","DOIUrl":null,"url":null,"abstract":"<p><p>Recent publications by Benet and coworkers, Korzekwa and Nagar, and Rowland et al. signal disagreement regarding the use of Kirchhoff's laws in combining pharmacokinetic parameters, especially clearances and rate constants. Here, it is pointed out that Kirchhoff's laws as applied to pharmacokinetics simply assert that concentrations are well defined and that molar or mass balances hold. The real issue is how to combine parameters for clearance processes in sequence, which may be reversible, irreversible, or even active in either or both directions. It is also demonstrated that Kirchhoff's laws cannot be used to resolve contradictory results observed in liver transport and clearance. Finally, a simple argument is provided relating nonlinear clearance to apparently anomalous bioavailability observations.</p>","PeriodicalId":50934,"journal":{"name":"AAPS Journal","volume":null,"pages":null},"PeriodicalIF":5.0000,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"AAPS Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1208/s12248-023-00875-6","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Recent publications by Benet and coworkers, Korzekwa and Nagar, and Rowland et al. signal disagreement regarding the use of Kirchhoff's laws in combining pharmacokinetic parameters, especially clearances and rate constants. Here, it is pointed out that Kirchhoff's laws as applied to pharmacokinetics simply assert that concentrations are well defined and that molar or mass balances hold. The real issue is how to combine parameters for clearance processes in sequence, which may be reversible, irreversible, or even active in either or both directions. It is also demonstrated that Kirchhoff's laws cannot be used to resolve contradictory results observed in liver transport and clearance. Finally, a simple argument is provided relating nonlinear clearance to apparently anomalous bioavailability observations.
期刊介绍：
The AAPS Journal, an official journal of the American Association of Pharmaceutical Scientists (AAPS), publishes novel and significant findings in the various areas of pharmaceutical sciences impacting human and veterinary therapeutics, including:
· Drug Design and Discovery
· Pharmaceutical Biotechnology
· Biopharmaceutics, Formulation, and Drug Delivery
· Metabolism and Transport
· Pharmacokinetics, Pharmacodynamics, and Pharmacometrics
· Translational Research
· Clinical Evaluations and Therapeutic Outcomes
· Regulatory Science
We invite submissions under the following article types:
· Original Research Articles
· Reviews and Mini-reviews
· White Papers, Commentaries, and Editorials
· Meeting Reports
· Brief/Technical Reports and Rapid Communications
· Regulatory Notes
· Tutorials
· Protocols in the Pharmaceutical Sciences
In addition, The AAPS Journal publishes themes, organized by guest editors, which are focused on particular areas of current interest to our field.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
