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Journal Article

Citation

Adachi K, Beppu S, Terashima M, Kobari W, Shimizu M, Yamazaki H. J. Pharm. Health Care Sci. 2021; 7(1).

Copyright

(Copyright © 2021, Holtzbrinck Springer Nature Publishing Group - BMC)

DOI

10.1186/s40780-021-00215-w

PMID

unavailable

Abstract

BACKGROUND: Although the over-the-counter H1 receptor antagonist diphenhydramine is not a common drug of abuse, it was recently recognized as one of the substances causing acute poisoning in patients attempting suicide that led to admissions to our hospital emergency room. Case presentation: Two patients [women aged 21 and 27 years (cases 1 and 2)] were emergently admitted after intentionally taking overdoses of 900 and 1200 mg diphenhydramine, respectively. The plasma diphenhydramine concentrations in case 1 were 977 and 425 ng/mL at 2.5 and 11.5 h after single oral overdose, and those in case 2 were 1320 and 475 ng/mL at 3 and 18 h after administration, respectively. We set up a simplified physiologically based pharmacokinetic (PBPK) model that was established using the reported pharmacokinetic data for a microdose of diphenhydramine. The two virtual plasma concentrations and the area under the curve (AUC) values extrapolated using the PBPK model were consistent with the observed overdose data. This finding implied linearity of pharmacokinetics over a wide dosage range for diphenhydramine.

CONCLUSIONS: The determined plasma concentrations of diphenhydramine of around 1000 ng/mL at ~ 3 h after orally administered overdoses in cases 1 and 2 may not have been high enough to cause hepatic impairment because levels of aspartate aminotransferase and alanine aminotransferase were normal; however, there was an increase in total bilirubin in case 1. Nonetheless, high virtual liver exposures of diphenhydramine were estimated by the current PBPK model. The present results based on drug monitoring data and pharmacokinetic predictions could serve as a useful guide when setting the duration of treatment in cases of diphenhydramine overdose. © 2021, The Author(s).


Language: en

Keywords

adult; human; female; case report; suicide attempt; drug overdose; prediction; blood sampling; clinical article; liquid chromatography; hospital admission; dose calculation; drug blood level; diphenhydramine; restlessness; acetonitrile; drug tissue level; heart rate; electrocardiogram; Glasgow coma scale; drug monitoring; body temperature; Liver damage; laboratory test; blood pressure; drug self administration; communication disorder; liver disease; QRS complex; Article; single drug dose; consciousness level; bilirubin; treatment duration; tandem mass spectrometry; young adult; breathing rate; QTc interval; Japanese (people); pharmacokinetic parameters; Ringer solution; absorption rate constant; Drug monitoring data; elimination rate constant; hepatic clearance; intrinsic clearance; kidney blood flow; liver blood flow; Pharmacokinetic prediction; substrate concentration; Total bilirubin

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