Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-01-01
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| Series: | Pharmaceutics |
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| Online Access: | http://www.mdpi.com/1999-4923/10/1/20 |
| _version_ | 1798006397853499392 |
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| author | Raúl Medina-López Nancy Vara-Gama Olivia Soria-Arteche Luis A. Moreno-Rocha Francisco J. López-Muñoz |
| author_facet | Raúl Medina-López Nancy Vara-Gama Olivia Soria-Arteche Luis A. Moreno-Rocha Francisco J. López-Muñoz |
| author_sort | Raúl Medina-López |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T12:55:21Z |
| format | Article |
| id | doaj.art-7afdc19064734b89a24e3ee88cf24f51 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T12:55:21Z |
| publishDate | 2018-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-7afdc19064734b89a24e3ee88cf24f512022-12-22T04:23:06ZengMDPI AGPharmaceutics1999-49232018-01-011012010.3390/pharmaceutics10010020pharmaceutics10010020Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic RatsRaúl Medina-López0Nancy Vara-Gama1Olivia Soria-Arteche2Luis A. Moreno-Rocha3Francisco J. López-Muñoz4Departamento Sistemas Biologicos Universidad Autonoma Metropolitana-Xochimilco, Calz. del Hueso 1100, Col. Villa Quietud, Mexico City 04960, MexicoDepartamento Sistemas Biologicos Universidad Autonoma Metropolitana-Xochimilco, Calz. del Hueso 1100, Col. Villa Quietud, Mexico City 04960, MexicoDepartamento Sistemas Biologicos Universidad Autonoma Metropolitana-Xochimilco, Calz. del Hueso 1100, Col. Villa Quietud, Mexico City 04960, MexicoDepartamento Sistemas Biologicos Universidad Autonoma Metropolitana-Xochimilco, Calz. del Hueso 1100, Col. Villa Quietud, Mexico City 04960, MexicoLaboratorio No. 7 “Dolor y Analgesia” del Departamento de Farmacobiologia, Cinvestav-Sede Sur, Calz. de los Tenorios No. 235, Col. Granjas Coapa, Mexico City 14330, MexicoThe 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.http://www.mdpi.com/1999-4923/10/1/20(S)-ketoprofencaffeinepharmacokineticspharmacodynamicsPIFIR model |
| spellingShingle | Raúl Medina-López Nancy Vara-Gama Olivia Soria-Arteche Luis A. Moreno-Rocha Francisco J. López-Muñoz Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats Pharmaceutics (S)-ketoprofen caffeine pharmacokinetics pharmacodynamics PIFIR model |
| title | Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats |
| title_full | Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats |
| title_fullStr | Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats |
| title_full_unstemmed | Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats |
| title_short | Pharmacokinetics and Pharmacodynamics of (S)-Ketoprofen Co-Administered with Caffeine: A Preclinical Study in Arthritic Rats |
| title_sort | pharmacokinetics and pharmacodynamics of s ketoprofen co administered with caffeine a preclinical study in arthritic rats |
| topic | (S)-ketoprofen caffeine pharmacokinetics pharmacodynamics PIFIR model |
| url | http://www.mdpi.com/1999-4923/10/1/20 |
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