Pharmacokinetics of loxoprofen in a self-administered overdose in a Japanese patient admitted to hospital
Abstract Background Loxoprofen is a propionic acid derivative and is the most widely prescribed non-steroidal anti-inflammatory drug in Japan. Loxoprofen is generally considered to be relatively nontoxic. Case presentation A 33-year-old man (body weight, 55 kg) who intentionally took an overdose of...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-09-01
|
| Series: | Journal of Pharmaceutical Health Care and Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40780-021-00216-9 |
| _version_ | 1819129320142012416 |
|---|---|
| author | Koichiro Adachi Yuki Sugitani Ryo Unita Kosuke Yoshida Satoru Beppu Mariko Terashima Masaya Fujii Makiko Shimizu Hiroshi Yamazaki |
| author_facet | Koichiro Adachi Yuki Sugitani Ryo Unita Kosuke Yoshida Satoru Beppu Mariko Terashima Masaya Fujii Makiko Shimizu Hiroshi Yamazaki |
| author_sort | Koichiro Adachi |
| collection | DOAJ |
| description | Abstract Background Loxoprofen is a propionic acid derivative and is the most widely prescribed non-steroidal anti-inflammatory drug in Japan. Loxoprofen is generally considered to be relatively nontoxic. Case presentation A 33-year-old man (body weight, 55 kg) who intentionally took an overdose of 100 tablets of loxoprofen (6000 mg) as a suicide attempt was emergently admitted to Kyoto Medical Center. On arrival, the patient was suffering disorders of consciousness. His plasma concentrations of loxoprofen and its reduced trans-alcohol metabolite were 52 and 24 μg/mL, 3.7 and 2.3 μg/mL, 0.81 and 0.54 μg/mL, and 0.015 and 0.011 μg/mL, respectively, at 4, 26, 50, and 121 h after the oral overdose. The observed apparent terminal elimination half-life of loxoprofen during days 1 and 2 of hospitalization was in the range 6–12 h, which is several times longer than the reported normal value. This finding implied nonlinearity of loxoprofen pharmacokinetics over the current 100-fold dose range, which could affect the accuracy of values simulated by a simplified physiologically based pharmacokinetic (PBPK) model founded on data from a normal dose of 60 mg. The reasons for the delayed eliminations from plasma of loxoprofen and its trans-alcohol metabolite in this case are uncertain, but slight renal impairment (low eGFR values) developed on the second and third hospital days and could be a causal factor. Conclusions Because the patient’s level of consciousness had gradually improved, he was discharged on the fourth day of hospitalization. The virtual plasma exposures of loxoprofen and its reduced trans-alcohol metabolite estimated using the current simplified PBPK model were lower than the measured values in the overdose case. The present results based on drug monitoring data and pharmacokinetic predictions could serve as a useful guide in cases of loxoprofen overdose. |
| first_indexed | 2024-12-22T08:41:50Z |
| format | Article |
| id | doaj.art-239879cb02d849f88f723896216f1ca7 |
| institution | Directory Open Access Journal |
| issn | 2055-0294 |
| language | English |
| last_indexed | 2024-12-22T08:41:50Z |
| publishDate | 2021-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Pharmaceutical Health Care and Sciences |
| spelling | doaj.art-239879cb02d849f88f723896216f1ca72022-12-21T18:32:13ZengBMCJournal of Pharmaceutical Health Care and Sciences2055-02942021-09-01711510.1186/s40780-021-00216-9Pharmacokinetics of loxoprofen in a self-administered overdose in a Japanese patient admitted to hospitalKoichiro Adachi0Yuki Sugitani1Ryo Unita2Kosuke Yoshida3Satoru Beppu4Mariko Terashima5Masaya Fujii6Makiko Shimizu7Hiroshi Yamazaki8Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical UniversityKyoto Medical CenterKyoto Medical CenterKyoto Medical CenterKyoto Medical CenterKyoto Medical CenterLaboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical UniversityLaboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical UniversityLaboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical UniversityAbstract Background Loxoprofen is a propionic acid derivative and is the most widely prescribed non-steroidal anti-inflammatory drug in Japan. Loxoprofen is generally considered to be relatively nontoxic. Case presentation A 33-year-old man (body weight, 55 kg) who intentionally took an overdose of 100 tablets of loxoprofen (6000 mg) as a suicide attempt was emergently admitted to Kyoto Medical Center. On arrival, the patient was suffering disorders of consciousness. His plasma concentrations of loxoprofen and its reduced trans-alcohol metabolite were 52 and 24 μg/mL, 3.7 and 2.3 μg/mL, 0.81 and 0.54 μg/mL, and 0.015 and 0.011 μg/mL, respectively, at 4, 26, 50, and 121 h after the oral overdose. The observed apparent terminal elimination half-life of loxoprofen during days 1 and 2 of hospitalization was in the range 6–12 h, which is several times longer than the reported normal value. This finding implied nonlinearity of loxoprofen pharmacokinetics over the current 100-fold dose range, which could affect the accuracy of values simulated by a simplified physiologically based pharmacokinetic (PBPK) model founded on data from a normal dose of 60 mg. The reasons for the delayed eliminations from plasma of loxoprofen and its trans-alcohol metabolite in this case are uncertain, but slight renal impairment (low eGFR values) developed on the second and third hospital days and could be a causal factor. Conclusions Because the patient’s level of consciousness had gradually improved, he was discharged on the fourth day of hospitalization. The virtual plasma exposures of loxoprofen and its reduced trans-alcohol metabolite estimated using the current simplified PBPK model were lower than the measured values in the overdose case. The present results based on drug monitoring data and pharmacokinetic predictions could serve as a useful guide in cases of loxoprofen overdose.https://doi.org/10.1186/s40780-021-00216-9Pharmacokinetic modelingOverdoseAbsorptionElimination |
| spellingShingle | Koichiro Adachi Yuki Sugitani Ryo Unita Kosuke Yoshida Satoru Beppu Mariko Terashima Masaya Fujii Makiko Shimizu Hiroshi Yamazaki Pharmacokinetics of loxoprofen in a self-administered overdose in a Japanese patient admitted to hospital Journal of Pharmaceutical Health Care and Sciences Pharmacokinetic modeling Overdose Absorption Elimination |
| title | Pharmacokinetics of loxoprofen in a self-administered overdose in a Japanese patient admitted to hospital |
| title_full | Pharmacokinetics of loxoprofen in a self-administered overdose in a Japanese patient admitted to hospital |
| title_fullStr | Pharmacokinetics of loxoprofen in a self-administered overdose in a Japanese patient admitted to hospital |
| title_full_unstemmed | Pharmacokinetics of loxoprofen in a self-administered overdose in a Japanese patient admitted to hospital |
| title_short | Pharmacokinetics of loxoprofen in a self-administered overdose in a Japanese patient admitted to hospital |
| title_sort | pharmacokinetics of loxoprofen in a self administered overdose in a japanese patient admitted to hospital |
| topic | Pharmacokinetic modeling Overdose Absorption Elimination |
| url | https://doi.org/10.1186/s40780-021-00216-9 |
| work_keys_str_mv | AT koichiroadachi pharmacokineticsofloxoprofeninaselfadministeredoverdoseinajapanesepatientadmittedtohospital AT yukisugitani pharmacokineticsofloxoprofeninaselfadministeredoverdoseinajapanesepatientadmittedtohospital AT ryounita pharmacokineticsofloxoprofeninaselfadministeredoverdoseinajapanesepatientadmittedtohospital AT kosukeyoshida pharmacokineticsofloxoprofeninaselfadministeredoverdoseinajapanesepatientadmittedtohospital AT satorubeppu pharmacokineticsofloxoprofeninaselfadministeredoverdoseinajapanesepatientadmittedtohospital AT marikoterashima pharmacokineticsofloxoprofeninaselfadministeredoverdoseinajapanesepatientadmittedtohospital AT masayafujii pharmacokineticsofloxoprofeninaselfadministeredoverdoseinajapanesepatientadmittedtohospital AT makikoshimizu pharmacokineticsofloxoprofeninaselfadministeredoverdoseinajapanesepatientadmittedtohospital AT hiroshiyamazaki pharmacokineticsofloxoprofeninaselfadministeredoverdoseinajapanesepatientadmittedtohospital |