{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T20:25:45Z","timestamp":1769631945417,"version":"3.49.0"},"reference-count":11,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,4]]},"abstract":"Abstract:<\/jats:title>\n A high activity of cytochrome P450 2D6 (CYP2D6) reportedly leads to toxicity of dihydrocodeine\/codeine by increasing toxic potential of their metabolite dihydromorphine\/morphine, which are further metabolized to highly active dihydromorphine 6-O<\/jats:italic>-glucuronide and the less active morphine 3-O<\/jats:italic>-glucorinide but rapidly excreted into urine as water-soluble forms. A case of acute respiratory depression after administration of prescribed dihydrocodeine phosphate (2.0 mg\/d divided twice a day for 2 days) to a 1-month-old baby boy genotyped as CYP2D6*1\/*10-*36<\/jats:italic> is described. The case is compared with that of a 14-year-old girl, also genotyped as CYP2D6*1\/*10-*36<\/jats:italic>, presenting in an agitated state after an overdose (37 mg) of dihydrocodeine phosphate taken as simultaneous ingestion of multiple over-the-counter tablets. In contrast to the rapid clearance of dihydrocodeine from blood in the 14-year-old girl (apparent half-life of 3 hours), the 1-month-old baby boy still had high serum concentrations of dihydrocodeine (400 nmol\/L) and dihydromorphine (1.9 nmol\/L) 21 hours after the last oral administration of dihydrocodeine-containing cough mixture. The rapid clearance in the 14-year-old girl was mainly attributed to dihydrocodeine glucuronidation and partly attributed to dihydromorphine formation, as determined by liquid chromatography\u2013tandem mass spectrometry analyses. However, the conjugation ratios of dihydrocodeine and dihydromorphine in the neonate were low in comparison with those in the 14-year-old girl and with those measured in 3-, 6-, and 13-year-old control subjects, resulting from the poorly developed glucuronidation potential of the neonate. The current observations suggest that the CYP2D6*1\/*10-*36<\/jats:italic> genotype seen in the 2 Japanese patients may not significantly contribute to the likelihood of dihydrocodeine overdose but highlight the importance of considering age when prescribing dihydrocodeine.<\/jats:p>","DOI":"10.1097\/ftd.0000000000000482","type":"journal-article","created":{"date-parts":[[2018,1,31]],"date-time":"2018-01-31T17:39:07Z","timestamp":1517420347000},"page":"162-165","source":"Crossref","is-referenced-by-count":10,"title":["Dihydrocodeine Overdoses in a Neonate and in a 14-year-old Girl Who Were Both Genotyped as Cytochrome P450 2D6*1\/*10-*36: Comparing Developmental Ages and Drug Monitoring Data With the Results of Pharmacokinetic Modeling"],"prefix":"10.1097","volume":"40","author":[{"given":"Makiko","family":"Shimizu","sequence":"first","affiliation":[{"name":"Showa Pharmaceutical University, Machida, Tokyo;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsuki","family":"Kondo","sequence":"additional","affiliation":[{"name":"Shizuoka Saiseikai General Hospital, Suruga-ku, Shizuoka; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetsuya","family":"Fukuoka","sequence":"additional","affiliation":[{"name":"Shizuoka Saiseikai General Hospital, Suruga-ku, Shizuoka; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiro","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Shizuoka Welfare Hospital, Aoi-ku, Shizuoka, Japan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Yamazaki","sequence":"additional","affiliation":[{"name":"Showa Pharmaceutical University, Machida, Tokyo;"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"R1-20230928","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/S0140-6736(06)69255-6","article-title":"Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother","volume":"368","author":"Koren","year":"2006","journal-title":"Lancet."},{"key":"R2-20230928","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1136\/archdischild-2014-307286","article-title":"Codeine in paediatrics: pharmacology, prescribing and controversies","volume":"101","author":"Andrzejowski","year":"2016","journal-title":"Arch Dis Child Educ Pract Ed."},{"key":"R3-20230928","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1007\/s00228-010-0876-4","article-title":"Limited effects of frequent CYP2D6*36-*10 tandem duplication allele on in vivo dextromethorphan metabolism in a Japanese population","volume":"66","author":"Kiyotani","year":"2010","journal-title":"Eur J Clin Pharmacol."},{"key":"R4-20230928","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1093\/jat\/31.7.394","article-title":"Method for quantification of opioids and their metabolites in autopsy blood by liquid chromatography-tandem mass spectrometry","volume":"31","author":"Al-Asmari","year":"2007","journal-title":"J Anal Toxicol."},{"key":"R5-20230928","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1093\/jat\/30.8.570","article-title":"Incomplete recovery of prescription opioids in urine using enzymatic hydrolysis of glucuronide metabolites","volume":"30","author":"Wang","year":"2006","journal-title":"J Anal Toxicol."},{"key":"R6-20230928","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1021\/acs.chemrestox.6b00136","article-title":"Combining chimeric mice with humanized liver, mass spectrometry, and physiologically-based pharmacokinetic modeling in toxicology","volume":"29","author":"Yamazaki","year":"2016","journal-title":"Chem Res Toxicol."},{"key":"R7-20230928","doi-asserted-by":"crossref","first-page":"95","DOI":"10.5414\/CPP41095","article-title":"The role of active metabolites in dihydrocodeine effects","volume":"41","author":"Schmidt","year":"2003","journal-title":"Int J Clin Pharmacol Ther."},{"key":"R8-20230928","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1046\/j.1442-200X.2001.01427.x","article-title":"Codeine ingestion and apparent life-threatening event in a neonate","volume":"43","author":"Tong","year":"2001","journal-title":"Pediatr Int."},{"key":"R9-20230928","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/psp4.12144","article-title":"Characterization of contributing factors to variability in morphine clearance through PBPK modeling implemented with OCT1 transporter","volume":"6","author":"Emoto","year":"2017","journal-title":"CPT Pharmacometrics Syst Pharmacol."},{"key":"R10-20230928","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1038\/sj.clpt.6100101","article-title":"Ontogeny of dextromethorphan O- and N-demethylation in the first year of life","volume":"81","author":"Blake","year":"2007","journal-title":"Clin Pharmacol Ther."},{"key":"R11-20230928","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1111\/j.1365-2125.1989.tb03548.x","article-title":"Morphine metabolism in children","volume":"28","author":"Choonara","year":"1989","journal-title":"Br J Clin Pharmacol."}],"container-title":["Therapeutic Drug Monitoring"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.lww.com\/00007691-201804000-00002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T01:06:30Z","timestamp":1695863190000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/00007691-201804000-00002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4]]},"references-count":11,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2018]]}},"URL":"https:\/\/doi.org\/10.1097\/ftd.0000000000000482","relation":{},"ISSN":["0163-4356"],"issn-type":[{"value":"0163-4356","type":"print"}],"subject":[],"published":{"date-parts":[[2018,4]]}}}