Pharmacokinetics of caffeine self-administered in overdose in a Japanese patient admitted to hospital
Abstract Background Caffeine (0.1 g) is used as a central nervous system stimulant and as a nontoxic phenotyping probe for cytochrome P450 1A2. However, an increasing number of suicide attempts by caffeine overdose have been recently reported. Case presentation A 25-year-old woman (body weight, 43 k...
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | Journal of Pharmaceutical Health Care and Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40780-021-00220-z |
| _version_ | 1818719151059894272 |
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| author | Koichiro Adachi Satoru Beppu Mariko Terashima Toshiaki Fukuda Jun Tomizawa Makiko Shimizu Hiroshi Yamazaki |
| author_facet | Koichiro Adachi Satoru Beppu Mariko Terashima Toshiaki Fukuda Jun Tomizawa Makiko Shimizu Hiroshi Yamazaki |
| author_sort | Koichiro Adachi |
| collection | DOAJ |
| description | Abstract Background Caffeine (0.1 g) is used as a central nervous system stimulant and as a nontoxic phenotyping probe for cytochrome P450 1A2. However, an increasing number of suicide attempts by caffeine overdose have been recently reported. Case presentation A 25-year-old woman (body weight, 43 kg) who intentionally took an overdose of 5.9 g caffeine as a suicide attempt was emergently admitted to Kyoto Medical Center. The plasma concentrations of caffeine and its primary metabolite, N-demethylated paraxanthine, in the current case were 100 and 7.3 μg/mL, 81 and 9.9 μg/mL, 63 and 12 μg/mL, and 21 and 14 μg/mL, at 12, 20, 30, and 56 h after oral overdose, respectively. The observed apparent terminal elimination half-life of caffeine during days 1 and 2 of hospitalization was 27 h, which is several times longer than the reported normal value. This finding implied nonlinearity of caffeine pharmacokinetics over such a wide dose range, which could affect the accuracy of values simulated by a simplified physiologically based pharmacokinetic model founded on a normal dose of 100 mg. Low serum potassium levels (2.9 and 3.5 mM) on days 1 and 2 may have been caused by the caffeine overdose in the current case. Conclusions The patient underwent infusion with bicarbonate Ringer’s solution and potassium chloride and was discharged on the third day of hospitalization despite taking a potentially lethal dose of caffeine. The virtual plasma exposures of caffeine estimated using the current simplified PBPK model were higher than the measured values. The present results based on drug monitoring data and additional pharmacokinetic predictions could serve as a useful guide in cases of caffeine overdose. |
| first_indexed | 2024-12-17T20:02:23Z |
| format | Article |
| id | doaj.art-968e5126ff304c06b60c1ee6cccad19b |
| institution | Directory Open Access Journal |
| issn | 2055-0294 |
| language | English |
| last_indexed | 2024-12-17T20:02:23Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Pharmaceutical Health Care and Sciences |
| spelling | doaj.art-968e5126ff304c06b60c1ee6cccad19b2022-12-21T21:34:26ZengBMCJournal of Pharmaceutical Health Care and Sciences2055-02942021-10-01711610.1186/s40780-021-00220-zPharmacokinetics of caffeine self-administered in overdose in a Japanese patient admitted to hospitalKoichiro Adachi0Satoru Beppu1Mariko Terashima2Toshiaki Fukuda3Jun Tomizawa4Makiko Shimizu5Hiroshi Yamazaki6Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical UniversityKyoto Medical Center, Fukakusa Mukaihata-choKyoto Medical Center, Fukakusa Mukaihata-choHimeji 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 Caffeine (0.1 g) is used as a central nervous system stimulant and as a nontoxic phenotyping probe for cytochrome P450 1A2. However, an increasing number of suicide attempts by caffeine overdose have been recently reported. Case presentation A 25-year-old woman (body weight, 43 kg) who intentionally took an overdose of 5.9 g caffeine as a suicide attempt was emergently admitted to Kyoto Medical Center. The plasma concentrations of caffeine and its primary metabolite, N-demethylated paraxanthine, in the current case were 100 and 7.3 μg/mL, 81 and 9.9 μg/mL, 63 and 12 μg/mL, and 21 and 14 μg/mL, at 12, 20, 30, and 56 h after oral overdose, respectively. The observed apparent terminal elimination half-life of caffeine during days 1 and 2 of hospitalization was 27 h, which is several times longer than the reported normal value. This finding implied nonlinearity of caffeine pharmacokinetics over such a wide dose range, which could affect the accuracy of values simulated by a simplified physiologically based pharmacokinetic model founded on a normal dose of 100 mg. Low serum potassium levels (2.9 and 3.5 mM) on days 1 and 2 may have been caused by the caffeine overdose in the current case. Conclusions The patient underwent infusion with bicarbonate Ringer’s solution and potassium chloride and was discharged on the third day of hospitalization despite taking a potentially lethal dose of caffeine. The virtual plasma exposures of caffeine estimated using the current simplified PBPK model were higher than the measured values. The present results based on drug monitoring data and additional pharmacokinetic predictions could serve as a useful guide in cases of caffeine overdose.https://doi.org/10.1186/s40780-021-00220-zPharmacokinetic modelingOverdoseSerum potassiumParaxanthine |
| spellingShingle | Koichiro Adachi Satoru Beppu Mariko Terashima Toshiaki Fukuda Jun Tomizawa Makiko Shimizu Hiroshi Yamazaki Pharmacokinetics of caffeine self-administered in overdose in a Japanese patient admitted to hospital Journal of Pharmaceutical Health Care and Sciences Pharmacokinetic modeling Overdose Serum potassium Paraxanthine |
| title | Pharmacokinetics of caffeine self-administered in overdose in a Japanese patient admitted to hospital |
| title_full | Pharmacokinetics of caffeine self-administered in overdose in a Japanese patient admitted to hospital |
| title_fullStr | Pharmacokinetics of caffeine self-administered in overdose in a Japanese patient admitted to hospital |
| title_full_unstemmed | Pharmacokinetics of caffeine self-administered in overdose in a Japanese patient admitted to hospital |
| title_short | Pharmacokinetics of caffeine self-administered in overdose in a Japanese patient admitted to hospital |
| title_sort | pharmacokinetics of caffeine self administered in overdose in a japanese patient admitted to hospital |
| topic | Pharmacokinetic modeling Overdose Serum potassium Paraxanthine |
| url | https://doi.org/10.1186/s40780-021-00220-z |
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