Effect of Ketorolac on Pharmacokinetics and Pharmacodynamics of 5-Fluorouracil: In Vivo and In Vitro Study
Background. This study aimed to evaluate the impact of ketorolac on the pharmacokinetics of 5-FU and its effect on the efficacy of 5-fluorouracil (5-FU) on the HT-29 cell line. Methods. Cell culture: the HT-29 cell line was treated with different concentrations of 5-FU, ketorolac, and combination of...
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| Format: | Article |
| Language: | English |
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Wiley
2022-01-01
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| Series: | Journal of Tropical Medicine |
| Online Access: | http://dx.doi.org/10.1155/2022/5267861 |
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| author | Motahare Atefinezhad Ahmadreza Moghadamnia Seyed Parsa Eftekhar Ali Akbar Moghadamnia Sohrab Kazemi |
| author_facet | Motahare Atefinezhad Ahmadreza Moghadamnia Seyed Parsa Eftekhar Ali Akbar Moghadamnia Sohrab Kazemi |
| author_sort | Motahare Atefinezhad |
| collection | DOAJ |
| description | Background. This study aimed to evaluate the impact of ketorolac on the pharmacokinetics of 5-FU and its effect on the efficacy of 5-fluorouracil (5-FU) on the HT-29 cell line. Methods. Cell culture: the HT-29 cell line was treated with different concentrations of 5-FU, ketorolac, and combination of 5-FU and ketorolac for 24 and 48 hours. The cell viability (%) was calculated by the MTT assay. Animal study: rats were randomly divided into control and pretreatment groups. The control group received physiological saline, whereas the pretreatment group received ketorolac by intraperitoneal (i.p.) injections on a daily basis for 14 days. On the 15th day, both groups received 5-FU (i.p.). Blood samples were collected at different times for HPLC analysis, and 5-FU pharmacokinetic parameters were calculated. Results. At cell culture study, in a certain concentration range, combination therapy showed synergistic effects (<0.05). However, at concentrations above this range, combination therapy showed antagonistic effects on 5-FU efficacy (<0.05). According to the pharmacokinetic analysis, pretreatment with ketorolac resulted in a significant increase in AUC, Cmax, and Tmax of 5-FU (<0.05) and a significant decrease in V/F and Cl/F of 5-FU (<0.05). Conclusions. Combination therapy with ketorolac and 5-FU, depending on time and concentration, has a synergistic effect on reducing the viability of cancer cells. Also, ketorolac is able to alter the pharmacokinetics of 5-FU. Since there is a close relationship between pharmacokinetic parameters of 5-FU and its effectiveness/toxicity, it seems that these changes are towards creating a synergistic effect on 5-FU cytotoxicity. These results suggest the need to optimize the dose of these drugs in order to increase clinical efficacy and reduce the toxicity associated with them. |
| format | Article |
| id | doaj-art-e57d7ad06d754592835e7a8dc8dce01c |
| institution | Kabale University |
| issn | 1687-9694 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Tropical Medicine |
| spelling | doaj-art-e57d7ad06d754592835e7a8dc8dce01c2025-08-20T03:26:20ZengWileyJournal of Tropical Medicine1687-96942022-01-01202210.1155/2022/5267861Effect of Ketorolac on Pharmacokinetics and Pharmacodynamics of 5-Fluorouracil: In Vivo and In Vitro StudyMotahare Atefinezhad0Ahmadreza Moghadamnia1Seyed Parsa Eftekhar2Ali Akbar Moghadamnia3Sohrab Kazemi4Department of PharmacologyStudent Research CommitteeDepartment of Pharmacology and ToxicologyDepartment of Pharmacology and ToxicologyCellular and Molecular Biology Research CenterBackground. This study aimed to evaluate the impact of ketorolac on the pharmacokinetics of 5-FU and its effect on the efficacy of 5-fluorouracil (5-FU) on the HT-29 cell line. Methods. Cell culture: the HT-29 cell line was treated with different concentrations of 5-FU, ketorolac, and combination of 5-FU and ketorolac for 24 and 48 hours. The cell viability (%) was calculated by the MTT assay. Animal study: rats were randomly divided into control and pretreatment groups. The control group received physiological saline, whereas the pretreatment group received ketorolac by intraperitoneal (i.p.) injections on a daily basis for 14 days. On the 15th day, both groups received 5-FU (i.p.). Blood samples were collected at different times for HPLC analysis, and 5-FU pharmacokinetic parameters were calculated. Results. At cell culture study, in a certain concentration range, combination therapy showed synergistic effects (<0.05). However, at concentrations above this range, combination therapy showed antagonistic effects on 5-FU efficacy (<0.05). According to the pharmacokinetic analysis, pretreatment with ketorolac resulted in a significant increase in AUC, Cmax, and Tmax of 5-FU (<0.05) and a significant decrease in V/F and Cl/F of 5-FU (<0.05). Conclusions. Combination therapy with ketorolac and 5-FU, depending on time and concentration, has a synergistic effect on reducing the viability of cancer cells. Also, ketorolac is able to alter the pharmacokinetics of 5-FU. Since there is a close relationship between pharmacokinetic parameters of 5-FU and its effectiveness/toxicity, it seems that these changes are towards creating a synergistic effect on 5-FU cytotoxicity. These results suggest the need to optimize the dose of these drugs in order to increase clinical efficacy and reduce the toxicity associated with them.http://dx.doi.org/10.1155/2022/5267861 |
| spellingShingle | Motahare Atefinezhad Ahmadreza Moghadamnia Seyed Parsa Eftekhar Ali Akbar Moghadamnia Sohrab Kazemi Effect of Ketorolac on Pharmacokinetics and Pharmacodynamics of 5-Fluorouracil: In Vivo and In Vitro Study Journal of Tropical Medicine |
| title | Effect of Ketorolac on Pharmacokinetics and Pharmacodynamics of 5-Fluorouracil: In Vivo and In Vitro Study |
| title_full | Effect of Ketorolac on Pharmacokinetics and Pharmacodynamics of 5-Fluorouracil: In Vivo and In Vitro Study |
| title_fullStr | Effect of Ketorolac on Pharmacokinetics and Pharmacodynamics of 5-Fluorouracil: In Vivo and In Vitro Study |
| title_full_unstemmed | Effect of Ketorolac on Pharmacokinetics and Pharmacodynamics of 5-Fluorouracil: In Vivo and In Vitro Study |
| title_short | Effect of Ketorolac on Pharmacokinetics and Pharmacodynamics of 5-Fluorouracil: In Vivo and In Vitro Study |
| title_sort | effect of ketorolac on pharmacokinetics and pharmacodynamics of 5 fluorouracil in vivo and in vitro study |
| url | http://dx.doi.org/10.1155/2022/5267861 |
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