We will investigate mechanisms involved in the incorporation of drugs of abuse into human hair. The pharmacokinetics of cocaine and methamphetamine in hair, skin, sweat and sebum, and plasma will be characterized so as to better understand mechanisms by which drugs enter hair. Multiple mechanisms and pathways involving skin tissues and skin secretions as possible reservoirs and transport vehicles for drugs will be considered. Skin is sometimes considered to be the largest organ of the body. Dose and time dependent concentrations, time course of uptake and disappearance, apparent partition coefficients and the relationships between the skin concentrations of drugs and major metabolites in various biofluid and tissue samples will be determined. We will determine how significant are sweat and sebaceous gland secretions for incorporation of drugs into hair and examine hair color and racial differences in the uptake of drugs into hair. Deuterium-labeled cocaine and methamphetamine will be administered to human volunteers and sequential plasma, urine, skin, sweat, and hair samples will be analyzed by gas chroma-tography and mass spectrometry. Drug and metabolite concentrations will be measured in skin punch biopsy specimens, stratum corneum, interstitial fluid, sebum, sweat and hair. Relationships between dose and the skin concentrations, skin pharmacological responses and hair levels will be determined. From these data, we will model the role of skin tissues and skin secretions in the transport of drugs into hair and sweat. The use of isotope-labeled drugs to control for residual stores of the drug in the body and surreptitious drug use by subjects will allow many months of outpatient study after a single dose given in a laboratory setting since illicit use of the labeled test drug will not interfere with following the course of the test dose. The research will provide useful scientific information for interpretation of hair and sweat and hair analysis as a biomarker for exposure to drugs and chemicals.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA010781-03
Application #
6174854
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Babecki, Beth
Project Start
1998-04-01
Project End
2001-12-31
Budget Start
2000-04-01
Budget End
2001-12-31
Support Year
3
Fiscal Year
2000
Total Cost
$331,128
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Uemura, Naoto; Nath, Rajneesh P; Harkey, Martha R et al. (2004) Cocaine levels in sweat collection patches vary by location of patch placement and decline over time. J Anal Toxicol 28:253-9
Lester, Laeben; Uemura, Naoto; Ademola, John et al. (2002) Disposition of cocaine in skin, interstitial fluid, sebum, and stratum corneum. J Anal Toxicol 26:547-53