Etodolac Single Dose Metabolic Profile Elucidation: Pharmacokinetics and Adverse Events in Healthy Volunteers
Background/Objectives: This study investigates the metabolic profile of a single dose of etodolac in healthy volunteers, focusing on pharmacokinetics, clinical parameters, and metabolomic variations to identify biomarkers and pathways linked to drug response, efficacy, and safety. Methods: Thirty-se...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/18/1/82 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832587717172527104 |
|---|---|
| author | Karen Sánchez-Luquez Anne Michelli Reis Silveira Salvador Sánchez-Vinces Alex Ap. Rosini Silva Joyce Barreto Rhubia Bethania Socorro Lemos de Brito Caroline de Moura Garcia Ana Lais Vieira Marcia Ap. Antonio Patrícia de Oliveira Carvalho |
| author_facet | Karen Sánchez-Luquez Anne Michelli Reis Silveira Salvador Sánchez-Vinces Alex Ap. Rosini Silva Joyce Barreto Rhubia Bethania Socorro Lemos de Brito Caroline de Moura Garcia Ana Lais Vieira Marcia Ap. Antonio Patrícia de Oliveira Carvalho |
| author_sort | Karen Sánchez-Luquez |
| collection | DOAJ |
| description | Background/Objectives: This study investigates the metabolic profile of a single dose of etodolac in healthy volunteers, focusing on pharmacokinetics, clinical parameters, and metabolomic variations to identify biomarkers and pathways linked to drug response, efficacy, and safety. Methods: Thirty-seven healthy volunteers, enrolled after rigorous health assessments, received a single dose of etodolac (Flancox<sup>®</sup> 500 mg). Pharmacokinetic profiles were determined using tandem mass spectrometry analysis, and the metabolomic profiling was conducted using baseline samples (pre-dose) and samples at maximum drug concentration (post-dose) via liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer. Network analysis was employed to interpret the data. Results: Correlations were observed between metabolomic profiles and pharmacokinetic parameters as well as clinical characteristics. Notably, metabolites derived from arachidonic acid, such as prostaglandins and leukotrienes, were linked to etodolac’s pharmacokinetics. Other metabolites involved in pathways like cholesterol biosynthesis, bile salts, riboflavin, and retinoic acid signaling were correlated with hematological and liver function parameters. These findings are consistent with the infrequent adverse events reported by participants, including hematological and biochemical changes in liver function. Conclusions: A set of metabolites was identified in possible associations between specific pathways and unusual side effects, comparing the metabolic profiles before and after doses of etodolac. Our results highlight the importance of optimizing drug therapy and minimizing adverse events by taking into account individual metabolic profile information. |
| format | Article |
| id | doaj-art-757b84a1d44c41c983d2af70f3864fe5 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-757b84a1d44c41c983d2af70f3864fe52025-01-24T13:45:19ZengMDPI AGPharmaceuticals1424-82472025-01-011818210.3390/ph18010082Etodolac Single Dose Metabolic Profile Elucidation: Pharmacokinetics and Adverse Events in Healthy VolunteersKaren Sánchez-Luquez0Anne Michelli Reis Silveira1Salvador Sánchez-Vinces2Alex Ap. Rosini Silva3Joyce Barreto4Rhubia Bethania Socorro Lemos de Brito5Caroline de Moura Garcia6Ana Lais Vieira7Marcia Ap. Antonio8Patrícia de Oliveira Carvalho9Health Sciences Postgraduate Program, São Francisco University—USF, Bragança Paulista 12916-900, SP, BrazilHealth Sciences Postgraduate Program, São Francisco University—USF, Bragança Paulista 12916-900, SP, BrazilHealth Sciences Postgraduate Program, São Francisco University—USF, Bragança Paulista 12916-900, SP, BrazilHealth Sciences Postgraduate Program, São Francisco University—USF, Bragança Paulista 12916-900, SP, BrazilIntegrated Unit of Pharmacology and Gastroenterology (UNIFAG), São Francisco University—USF, Bragança Paulista 12916-900, SP, BrazilAlthaia S.A. Indústria Farmacêutica, Atibaia 12952-820, SP, BrazilAlthaia S.A. Indústria Farmacêutica, Atibaia 12952-820, SP, BrazilAlthaia S.A. Indústria Farmacêutica, Atibaia 12952-820, SP, BrazilIntegrated Unit of Pharmacology and Gastroenterology (UNIFAG), São Francisco University—USF, Bragança Paulista 12916-900, SP, BrazilHealth Sciences Postgraduate Program, São Francisco University—USF, Bragança Paulista 12916-900, SP, BrazilBackground/Objectives: This study investigates the metabolic profile of a single dose of etodolac in healthy volunteers, focusing on pharmacokinetics, clinical parameters, and metabolomic variations to identify biomarkers and pathways linked to drug response, efficacy, and safety. Methods: Thirty-seven healthy volunteers, enrolled after rigorous health assessments, received a single dose of etodolac (Flancox<sup>®</sup> 500 mg). Pharmacokinetic profiles were determined using tandem mass spectrometry analysis, and the metabolomic profiling was conducted using baseline samples (pre-dose) and samples at maximum drug concentration (post-dose) via liquid chromatography coupled with a quadrupole time-of-flight mass spectrometer. Network analysis was employed to interpret the data. Results: Correlations were observed between metabolomic profiles and pharmacokinetic parameters as well as clinical characteristics. Notably, metabolites derived from arachidonic acid, such as prostaglandins and leukotrienes, were linked to etodolac’s pharmacokinetics. Other metabolites involved in pathways like cholesterol biosynthesis, bile salts, riboflavin, and retinoic acid signaling were correlated with hematological and liver function parameters. These findings are consistent with the infrequent adverse events reported by participants, including hematological and biochemical changes in liver function. Conclusions: A set of metabolites was identified in possible associations between specific pathways and unusual side effects, comparing the metabolic profiles before and after doses of etodolac. Our results highlight the importance of optimizing drug therapy and minimizing adverse events by taking into account individual metabolic profile information.https://www.mdpi.com/1424-8247/18/1/82etodolacmetabolomics profilemetabolic pathwayspharmacokinetics |
| spellingShingle | Karen Sánchez-Luquez Anne Michelli Reis Silveira Salvador Sánchez-Vinces Alex Ap. Rosini Silva Joyce Barreto Rhubia Bethania Socorro Lemos de Brito Caroline de Moura Garcia Ana Lais Vieira Marcia Ap. Antonio Patrícia de Oliveira Carvalho Etodolac Single Dose Metabolic Profile Elucidation: Pharmacokinetics and Adverse Events in Healthy Volunteers Pharmaceuticals etodolac metabolomics profile metabolic pathways pharmacokinetics |
| title | Etodolac Single Dose Metabolic Profile Elucidation: Pharmacokinetics and Adverse Events in Healthy Volunteers |
| title_full | Etodolac Single Dose Metabolic Profile Elucidation: Pharmacokinetics and Adverse Events in Healthy Volunteers |
| title_fullStr | Etodolac Single Dose Metabolic Profile Elucidation: Pharmacokinetics and Adverse Events in Healthy Volunteers |
| title_full_unstemmed | Etodolac Single Dose Metabolic Profile Elucidation: Pharmacokinetics and Adverse Events in Healthy Volunteers |
| title_short | Etodolac Single Dose Metabolic Profile Elucidation: Pharmacokinetics and Adverse Events in Healthy Volunteers |
| title_sort | etodolac single dose metabolic profile elucidation pharmacokinetics and adverse events in healthy volunteers |
| topic | etodolac metabolomics profile metabolic pathways pharmacokinetics |
| url | https://www.mdpi.com/1424-8247/18/1/82 |
| work_keys_str_mv | AT karensanchezluquez etodolacsingledosemetabolicprofileelucidationpharmacokineticsandadverseeventsinhealthyvolunteers AT annemichellireissilveira etodolacsingledosemetabolicprofileelucidationpharmacokineticsandadverseeventsinhealthyvolunteers AT salvadorsanchezvinces etodolacsingledosemetabolicprofileelucidationpharmacokineticsandadverseeventsinhealthyvolunteers AT alexaprosinisilva etodolacsingledosemetabolicprofileelucidationpharmacokineticsandadverseeventsinhealthyvolunteers AT joycebarreto etodolacsingledosemetabolicprofileelucidationpharmacokineticsandadverseeventsinhealthyvolunteers AT rhubiabethaniasocorrolemosdebrito etodolacsingledosemetabolicprofileelucidationpharmacokineticsandadverseeventsinhealthyvolunteers AT carolinedemouragarcia etodolacsingledosemetabolicprofileelucidationpharmacokineticsandadverseeventsinhealthyvolunteers AT analaisvieira etodolacsingledosemetabolicprofileelucidationpharmacokineticsandadverseeventsinhealthyvolunteers AT marciaapantonio etodolacsingledosemetabolicprofileelucidationpharmacokineticsandadverseeventsinhealthyvolunteers AT patriciadeoliveiracarvalho etodolacsingledosemetabolicprofileelucidationpharmacokineticsandadverseeventsinhealthyvolunteers |