Vaginal drug distribution modeling.
This review presents and applies fundamental mass transport theory describing the diffusion and convection driven mass transport of drugs to the vaginal environment. It considers sources of variability in the predictions of the models. It illustrates use of model predictions of microbicide drug concentration distribution (pharmacokinetics) to gain insights about drug effectiveness in preventing HIV infection (pharmacodynamics). The modeling compares vaginal drug distributions after different gel dosage regimens, and it evaluates consequences of changes in gel viscosity due to aging. It compares vaginal mucosal concentration distributions of drugs delivered by gels vs. intravaginal rings. Finally, the modeling approach is used to compare vaginal drug distributions across species with differing vaginal dimensions. Deterministic models of drug mass transport into and throughout the vaginal environment can provide critical insights about the mechanisms and determinants of such transport. This knowledge, and the methodology that obtains it, can be applied and translated to multiple applications, involving the scientific underpinnings of vaginal drug distribution and the performance evaluation and design of products, and their dosage regimens, that achieve it.
Department of Biomedical Engineering, Duke University, Durham, NC, USA; Department of Obstetrics and Gynecology, Duke University, Durham, NC USA. Electronic address: dkatz@duke.edu.
David F
DF
Katz
Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Andrew
A
Yuan
Department of Biomedical Engineering, Duke University, Durham, NC, USA.
Yajing
Y
Gao
D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004355:Drug Stability; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008954:Models, Biological; D014621:Vagina / Q000033:anatomy & histology / Q000502:physiology; D066228:Vaginal Absorption / Q000502:physiology; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014783:Viscosity
D019380:Anti-HIV Agents; D014622:Vaginal Creams, Foams, and Jellies
Gel; HIV; Microbicides; Modeling; Mucosa; Ring; Vagina