The Pharmacokinetics of Morphine and Codeine in Human Plasma and Urine after Oral Administration of Qiangli Pipa Syrup

J Forensic Sci. 2018 Jul;63(4):1221-1228. doi: 10.1111/1556-4029.13696. Epub 2017 Nov 17.

Abstract

Papaveris pericarpium, a natural source of morphine and codeine, is the principal active component in many antitussive traditional Chinese medicines. We herein report the first PK study of papaveris pericarpium in human plasma and urine following oral administration of single (15, 30, 60 mL) and multiple dose (15 mL) of Qiangli Pipa Syrup (MOR 0.1 mg/mL, COD 0.028 mg/mL) by monitoring morphine and codeine using a HPLC-MS/MS method. Their Tmax and t1/2 values are independent of dosages, while the AUC0-t linearly increased with higher dosages, indicating linear PK characteristics. AUC0-t increased obviously after multiple doses, indicating possible risk of accumulative toxicity. Urine studies suggested risks of positive opiate drug tests with a cutoff of 300 ng/mL, which lasted 6-14 h at different doses. These results provide important information for clinical safety, efficacy and rational drug use of Qiangli Pipa Syrup and also guide the related judicial expertise of its administration.

Keywords: papaveris pericarpium; codeine; forensic science; human plasma; judicial expertise; morphine; pharmacokinetics; urine.

MeSH terms

  • Administration, Oral
  • Adult
  • Antitussive Agents / administration & dosage*
  • Antitussive Agents / chemistry
  • China
  • Chromatography, High Pressure Liquid
  • Codeine / analysis
  • Codeine / pharmacokinetics*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / administration & dosage*
  • Drugs, Chinese Herbal / chemistry
  • Humans
  • Male
  • Medicine, Chinese Traditional
  • Morphine / analysis
  • Morphine / pharmacokinetics*
  • Random Allocation
  • Tandem Mass Spectrometry
  • Young Adult

Substances

  • Antitussive Agents
  • Drugs, Chinese Herbal
  • Morphine
  • Codeine