Next Article in Journal
Stryphnodendron Species Known as “Barbatimão”: A Comprehensive Report
Previous Article in Journal
PKIDB: A Curated, Annotated and Updated Database of Protein Kinase Inhibitors in Clinical Trials
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle
Molecules 2018, 23(4), 909; https://doi.org/10.3390/molecules23040909

Pharmacokinetic–Pharmacodynamic Model for the Testosterone-Suppressive Effect of Leuprolide in Normal and Prostate Cancer Rats

1
College of Pharmacy, CHA University, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do 13488, Korea
2
College of Pharmacy, Chonnam National University, 77 Yongbong-ro, Buk-Gu, Gwangju 61186, Korea
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 27 February 2018 / Revised: 3 April 2018 / Accepted: 12 April 2018 / Published: 15 April 2018
Full-Text   |   PDF [3240 KB, uploaded 3 May 2018]   |  

Abstract

This study developed the pharmacokinetic (PK)–pharmacodynamic (PD) model of the testosterone-suppressive effect of leuprolide for evaluation of the sustained release (SR) depot and leuprolide solution in rats with or without prostate cancer. Six groups of rats were divided by the routes of administration (intravenous and subcutaneous injection) and kinds of formulation (vehicle, leuprolide solution, and SR depot). The PK profile after subcutaneous injection of leuprolide solution could be well-described by the one-compartment model. The absorption rate constant, the total body clearance, and the volume of distribution were estimated at 16.67 h−1, 514.46 mL/h, and 487.40 mL. Using PK parameters in the solution-administered group, the PK model for the SR depot was developed. The PK–PD model was constructed by describing the testosterone-suppressive effect of leuprolide using the feedback turnover model. The response of testosterone after administration of each formulation was well described using this PK–PD model for the estimation of PD parameters (EC50, Emax, h) and systemic parameters (kin, kout, kf on, kf off). The developed PK–PD model containing an inhibitory feedback system could successfully describe the testosterone-suppressive effect of leuprolide in the type of formulation. The PK–PD model developed would be useful for evaluating the formulation of similar drugs whose effect is regulated through the feedback mechanism. View Full-Text
Keywords: leuprolide; sustained release depot; pharmacokinetics; pharmacodynamics; pharmacokinetic–pharmacodynamic model leuprolide; sustained release depot; pharmacokinetics; pharmacodynamics; pharmacokinetic–pharmacodynamic model
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Lee, D.-S.; Kim, S.-J.; Choi, G.-W.; Lee, Y.-B.; Cho, H.-Y. Pharmacokinetic–Pharmacodynamic Model for the Testosterone-Suppressive Effect of Leuprolide in Normal and Prostate Cancer Rats. Molecules 2018, 23, 909.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top