B-276 Excretion of codeine in human fingerprint sweat and pharmacokinetics following controlled oral codeine administration

Background The detection of prescription and/or recreational drugs is important to ensure workplace safety, to enforce judicial actions, and to monitor detoxification. Drugs and drug metabolites are expressed in blood, urine, and oral fluid such that those specimens can be used to detect recent drug use. These specimen matrices offer varying degrees of privacy and invasiveness to the subject. In addition, the ease-of-use in workplace settings varies in terms of convenience, infrastructure requirements, and procedural controls. Sweat patches have been proposed to provide a record of an individual’s drug use, but these typically are worn for one week or longer. Analysis of fingerprint sweat offers a more convenient method of drug detection. This study assessed the comparative profiling of codeine in human fingerprint sweat following controlled codeine administration under naltrexone blockade in the clinic. Methods Thirty-nine healthy adults, including male and non-pregnant female subjects, completed a clinical trial under an ethics board-approved protocol. Each subject received three 60 mg codeine phosphate doses, with four hours between doses. To prevent any opioid effects, each subject received three 50 mg doses of naltrexone hydrochloride: 12 hours, one hour prior, and 12 hours after the first codeine phosphate administration. Fingerprint sweat, blood, and oral fluid specimens were collected at eighteen time points per subject for codeine analysis, beginning at 90 minutes prior to the first codeine phosphate dosage, with the final collection point at 24 hours after the initial codeine dosage. Specimens were collected in order of fingerprint sweat, oral fluid, and blood. Urine specimens were collected ad libitum. Codeine in fingerprint sweat, whole blood, oral fluid, and urine was determined using a validated LC-MS/MS method. Pharmacokinetic parameters were calculated using noncompartmental analysis with PKanalix version 2023R1, Lixoft SAS, a Simulations Plus company. Results Codeine in fingerprint sweat and oral fluid follows the trend seen in whole blood, most notably in response to the three doses of 60 mg codeine phosphate administered at 0, 4, and 8 hours. The concentration versus time profile of codeine in whole blood and fingerprint sweat shows that codeine was first detected in blood and fingerprint within approximately 30 minutes after oral administration of codeine. The calculated Tmax (with standard error) for the first codeine dosage in whole blood, fingerprint sweat, oral fluid, and urine are 1.96 (0.74), 2.08 (0.88), 1.73 (0.85), and 2.20 (1.17) hours, respectively. PK parameters for the excretion of codeine in the terminal phase of the study also compared favorably. Furthermore, PK parameters for this study show broad agreement with published results for blood and oral fluid. Conclusion The time course of mean codeine in fingerprint sweat follows the same response profile as for mean codeine in whole blood and oral fluid. PK parameters computed for codeine in fingerprint sweat, whole blood, oral fluid and urine show broad agreement and statistical agreement for Tmax during the first four hours following oral ingestion of 60 mg codeine, and for T1/2 during the terminal phase of the study following the third dose of codeine.