Next Article in Journal
Extended Duration Vascular Endothelial Growth Factor Inhibition in the Eye: Failures, Successes, and Future Possibilities
Previous Article in Journal
Minoxidil Skin Delivery from Nanoemulsion Formulations Containing Eucalyptol or Oleic Acid: Enhanced Diffusivity and Follicular Targeting
Previous Article in Special Issue
Development of a Region-Specific Physiologically Based Pharmacokinetic Brain Model to Assess Hippocampus and Frontal Cortex Pharmacokinetics
Article Menu
Issue 1 (March) cover image

Export Article

Open AccessArticle
Pharmaceutics 2018, 10(1), 20; https://doi.org/10.3390/pharmaceutics10010020

Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats

1
Departamento Sistemas Biologicos Universidad Autonoma Metropolitana-Xochimilco, Calz. del Hueso 1100, Col. Villa Quietud, Mexico City 04960, Mexico
2
Laboratorio No. 7 “Dolor y Analgesia” del Departamento de Farmacobiologia, Cinvestav-Sede Sur, Calz. de los Tenorios No. 235, Col. Granjas Coapa, Mexico City 14330, Mexico
*
Author to whom correspondence should be addressed.
Received: 31 October 2017 / Revised: 16 January 2018 / Accepted: 23 January 2018 / Published: 26 January 2018
(This article belongs to the Special Issue Preclinical Pharmacokinetics and Bioanalysis)
View Full-Text   |   Download PDF [545 KB, uploaded 26 January 2018]   |  

Abstract

The purpose of the present study was to determine whether caffeine modifies the pharmacokinetics and pharmacodynamics of (S)-ketoprofen following oral administration in a gout-type pain model. 3.2 mg/kg of (S)-ketoprofen alone and combined with 17.8 mg/kg of caffeine were administered to Wistar rats and plasma levels were determined between 0.5 and 24.0 h. Additionally, antinociception was evaluated based on the protocol of the PIFIR (pain-induced functional impairment in the rat) model before blood sampling between 0.5 and 4.0 h. Significant differences in Cmax, AUC0-24, and AUC0-∞ values were observed with caffeine administration (p < 0.05). Also, significant differences in Emax, Tmax, and AUC0-4 values were determined when comparing the treatments with and without caffeine (p < 0.05). By relating the pharmacokinetic and pharmacodynamic data, a counter-clockwise hysteresis loop was observed regardless of the administration of caffeine. When the relationship between AUCe and AUCp was fitted to the sigmoidal Emax model, a satisfactory correlation was found (R2 > 0.99) as well as significant differences in Emax and EC50 values (p < 0.05). With caffeine, Emax and EC50 values changed by 489.5% and 695.4%, respectively. The combination studied represents a convenient alternative for the treatment of pain when considering the advantages offered by using drugs with different mechanisms of action. View Full-Text
Keywords: (S)-ketoprofen; caffeine; pharmacokinetics; pharmacodynamics; PIFIR model (S)-ketoprofen; caffeine; pharmacokinetics; pharmacodynamics; PIFIR 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).

Share & Cite This Article

MDPI and ACS Style

Medina-López, R.; Vara-Gama, N.; Soria-Arteche, O.; Moreno-Rocha, L.A.; López-Muñoz, F.J. Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats. Pharmaceutics 2018, 10, 20.

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]
Pharmaceutics EISSN 1999-4923 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top