{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T20:20:55Z","timestamp":1784319655174,"version":"3.55.0"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2018,1,26]],"date-time":"2018-01-26T00:00:00Z","timestamp":1516924800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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-\u221e values were observed with caffeine administration (p &lt; 0.05). Also, significant differences in Emax, Tmax, and AUC0-4 values were determined when comparing the treatments with and without caffeine (p &lt; 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 &gt; 0.99) as well as significant differences in Emax and EC50 values (p &lt; 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics10010020","type":"journal-article","created":{"date-parts":[[2018,1,26]],"date-time":"2018-01-26T11:29:02Z","timestamp":1516966142000},"page":"20","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4159-8403","authenticated-orcid":false,"given":"Ra\u00fal","family":"Medina-L\u00f3pez","sequence":"first","affiliation":[{"name":"Departamento Sistemas Biologicos Universidad Autonoma Metropolitana-Xochimilco, Calz. del Hueso 1100, Col. Villa Quietud, Mexico City 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Vara-Gama","sequence":"additional","affiliation":[{"name":"Departamento Sistemas Biologicos Universidad Autonoma Metropolitana-Xochimilco, Calz. del Hueso 1100, Col. Villa Quietud, Mexico City 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Soria-Arteche","sequence":"additional","affiliation":[{"name":"Departamento Sistemas Biologicos Universidad Autonoma Metropolitana-Xochimilco, Calz. del Hueso 1100, Col. Villa Quietud, Mexico City 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Moreno-Rocha","sequence":"additional","affiliation":[{"name":"Departamento Sistemas Biologicos Universidad Autonoma Metropolitana-Xochimilco, Calz. del Hueso 1100, Col. Villa Quietud, Mexico City 04960, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"L\u00f3pez-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Laboratorio No. 7 \u201cDolor y Analgesia\u201d del Departamento de Farmacobiologia, Cinvestav-Sede Sur, Calz. de los Tenorios No. 235, Col. Granjas Coapa, Mexico City 14330, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,1,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1007\/s11095-008-9717-x","article-title":"PK\/PD modelling and beyond: Impact on drug development","volume":"25","author":"Breimer","year":"2008","journal-title":"Pharm. 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