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Pharmacokinetics of loxoprofen in a self-administered overdose in a Japanese patient admitted to hospital
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 tab...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422741/ https://www.ncbi.nlm.nih.gov/pubmed/34488903 http://dx.doi.org/10.1186/s40780-021-00216-9 |
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author | Adachi, Koichiro Sugitani, Yuki Unita, Ryo Yoshida, Kosuke Beppu, Satoru Terashima, Mariko Fujii, Masaya Shimizu, Makiko Yamazaki, Hiroshi |
author_facet | Adachi, Koichiro Sugitani, Yuki Unita, Ryo Yoshida, Kosuke Beppu, Satoru Terashima, Mariko Fujii, Masaya Shimizu, Makiko Yamazaki, Hiroshi |
author_sort | Adachi, Koichiro |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-8422741 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-84227412021-09-09 Pharmacokinetics of loxoprofen in a self-administered overdose in a Japanese patient admitted to hospital Adachi, Koichiro Sugitani, Yuki Unita, Ryo Yoshida, Kosuke Beppu, Satoru Terashima, Mariko Fujii, Masaya Shimizu, Makiko Yamazaki, Hiroshi J Pharm Health Care Sci Case Report 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. BioMed Central 2021-09-07 /pmc/articles/PMC8422741/ /pubmed/34488903 http://dx.doi.org/10.1186/s40780-021-00216-9 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Case Report Adachi, Koichiro Sugitani, Yuki Unita, Ryo Yoshida, Kosuke Beppu, Satoru Terashima, Mariko Fujii, Masaya Shimizu, Makiko Yamazaki, Hiroshi Pharmacokinetics of loxoprofen in a self-administered overdose in a Japanese patient admitted to hospital |
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 | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422741/ https://www.ncbi.nlm.nih.gov/pubmed/34488903 http://dx.doi.org/10.1186/s40780-021-00216-9 |
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