Skip to main content
release_alert
Welcome to the new Scholars 3.0! Read about new features and let us know what you think.
cancel
Journal cover image

Sensitivity Analysis of a Pharmacokinetic Model of Vaginal Anti-HIV Microbicide Drug Delivery.

Publication ,  Journal Article
Jarrett, AM; Gao, Y; Hussaini, MY; Cogan, NG; Katz, DF
Published in: Journal of Pharmaceutical Sciences
May 2016

Uncertainties in parameter values in microbicide pharmacokinetics (PK) models confound the models' use in understanding the determinants of drug delivery and in designing and interpreting dosing and sampling in PK studies. A global sensitivity analysis (Sobol' indices) was performed for a compartmental model of the pharmacokinetics of gel delivery of tenofovir to the vaginal mucosa. The model's parameter space was explored to quantify model output sensitivities to parameters characterizing properties for the gel-drug product (volume, drug transport, initial loading) and host environment (thicknesses of the mucosal epithelium and stroma and the role of ambient vaginal fluid in diluting gel). Greatest sensitivities overall were to the initial drug concentration in gel, gel-epithelium partition coefficient for drug, and rate constant for gel dilution by vaginal fluid. Sensitivities for 3 PK measures of drug concentration values were somewhat different than those for the kinetic PK measure. Sensitivities in the stromal compartment (where tenofovir acts against host cells) and a simulated biopsy also depended on thicknesses of epithelium and stroma. This methodology and results here contribute an approach to help interpret uncertainties in measures of vaginal microbicide gel properties and their host environment. In turn, this will inform rational gel design and optimization.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Journal of Pharmaceutical Sciences

DOI

EISSN

1520-6017

ISSN

0022-3549

Publication Date

May 2016

Volume

105

Issue

5

Start / End Page

1772 / 1778

Related Subject Headings

  • Vagina
  • Tenofovir
  • Pharmacology & Pharmacy
  • Models, Biological
  • Humans
  • Female
  • Drug Delivery Systems
  • Computer Simulation
  • Antiviral Agents
  • Anti-Infective Agents, Local
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Jarrett, A. M., Gao, Y., Hussaini, M. Y., Cogan, N. G., & Katz, D. F. (2016). Sensitivity Analysis of a Pharmacokinetic Model of Vaginal Anti-HIV Microbicide Drug Delivery. Journal of Pharmaceutical Sciences, 105(5), 1772–1778. https://doi.org/10.1016/j.xphs.2016.02.015
Jarrett, Angela M., Yajing Gao, M Yousuff Hussaini, Nicholas G. Cogan, and David F. Katz. “Sensitivity Analysis of a Pharmacokinetic Model of Vaginal Anti-HIV Microbicide Drug Delivery.Journal of Pharmaceutical Sciences 105, no. 5 (May 2016): 1772–78. https://doi.org/10.1016/j.xphs.2016.02.015.
Jarrett AM, Gao Y, Hussaini MY, Cogan NG, Katz DF. Sensitivity Analysis of a Pharmacokinetic Model of Vaginal Anti-HIV Microbicide Drug Delivery. Journal of Pharmaceutical Sciences. 2016 May;105(5):1772–8.
Jarrett, Angela M., et al. “Sensitivity Analysis of a Pharmacokinetic Model of Vaginal Anti-HIV Microbicide Drug Delivery.Journal of Pharmaceutical Sciences, vol. 105, no. 5, May 2016, pp. 1772–78. Epmc, doi:10.1016/j.xphs.2016.02.015.
Jarrett AM, Gao Y, Hussaini MY, Cogan NG, Katz DF. Sensitivity Analysis of a Pharmacokinetic Model of Vaginal Anti-HIV Microbicide Drug Delivery. Journal of Pharmaceutical Sciences. 2016 May;105(5):1772–1778.
Journal cover image

Published In

Journal of Pharmaceutical Sciences

DOI

EISSN

1520-6017

ISSN

0022-3549

Publication Date

May 2016

Volume

105

Issue

5

Start / End Page

1772 / 1778

Related Subject Headings

  • Vagina
  • Tenofovir
  • Pharmacology & Pharmacy
  • Models, Biological
  • Humans
  • Female
  • Drug Delivery Systems
  • Computer Simulation
  • Antiviral Agents
  • Anti-Infective Agents, Local