Incorporation of methamphetamine and amphetamine in human hair following controlled oral methamphetamine administration

Background: Although hair testing is well established for the assessment of past drug exposure, uncer-tainties persist about mechanisms of drug incorporation into hair and interpretation of results. The aim of this study was to administer methamphetamine (MAMP) under controlled conditions as a model drug to investigate drug incorporation into human hair. Material and methods: Seven volunteers with a history of stimulant use received 4 7 10 mg (low) doses of sustained release S-(+)-MAMP HCl within 1 week, with weekly head hair samples collected by shaving. 3 weeks later, 4 of them received 4 7 20 mg (high) doses. After extensive isopropanol/phosphate buffer washing of the hair, MAMP and its metabolite amphetamine (AMP) concentrations were determined in all weekly hair samples by LC\u2013MS\u2013MS in selected reaction monitoring mode with the undeca- and deca-deuterated drugs, respectively, as internal standards (LLOQ, 0.005 ng mg 121). Results: MAMP Tmaxoccurred from 1 to 2 weeks after both doses, with Cmaxranging from 0.6 to 3.5 ng mg 121 after the low and 1.2 to 5.3 ng mg 121 after the high MAMP doses. AMP Cmaxin hair was 0.1\u20130.3 ng mg 121 and 0.2\u20130.5 ng mg 121 , respectively, for low and high doses. Highly dose-related concentrations within subjects, but large variability between subjects were observed. MAMP concentrations were above the 0.2 ng mg 121 cut-off for at least 2 weeks following administration of both low and high doses. The overall AMP/MAMP ratio ranged from 0.07 to 0.37 with a mean value of 0.15 \ub1 0.07, and a median of 0.13. The percentage of MAMP and AMP removed with the washing procedure decreased with time after administration. A strong correlation was found between area under the curve of MAMP (r2 = 0.90, p = 0.00) and AMP (r2 = 0.94, p = 0.00) concentrations calculated for the 3-week period following administration and the total melanin concentration in hair. Significant correlations were observed also between Cmaxand melanin. Conclusions: This study demonstrated that despite large inter-individual differences, the incorporation of MAMP and AMP into hair is dose-related with much of the observed scatter of MAMP and AMP concentrations explained by melanin concentration in hai

Hypo-osmolar rectal douche tenofovir formulation prevents simian/human immunodeficiency virus acquisition in macaques

In spite of the rollout of oral pre-exposure prophylaxis (PrEP), the rate of new HIV infections remains a major health crisis. In the United States, new infections occur predominantly in men having sex with men (MSM) in rural settings where access to PrEP can be limited. As an alternative congruent with MSM sexual behavior, we have optimized and tested tenofovir (TFV) and analog-based iso-osmolar and hypo-osmolar (HOsm) rectal douches for efficacy against rectal simian/human immunodeficiency virus (SHIV) infection of macaques. Single TFV HOsm high-dose douches achieved peak plasma TFV levels similar to daily oral PrEP, while other formulations yielded lower concentrations. Rectal tissue TFV-diphosphate (TFV-DP) concentrations at the portal of virus entry, however, were markedly higher after HOsm douching than daily oral PrEP. Repeated douches led to significantly higher plasma TFV and higher TFV-DP concentrations in rectal tissue at 24 hours compared with single douches, without detectable mucosal or systemic toxicity. Using stringent repeated intrarectal SHIV exposures, single HOsm high-dose douches delivered greater protection from virus acquisition for more than 24 hours compared with oral PrEP. Our results demonstrate a rapid delivery of protective TFV doses to the rectal portal of virus entry as a potential low-cost and safe PrEP alternative. © 2022, Xiao et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]