The presence of cocaine was confirmed in the saliva of two male human subjects who had received intravenous doses of cocaine. For one subject, the saliva:plasma concentration ratios varied from 2.96 to 0.5 over time following drug administration. Correlations of saliva to plasma cocaine levels were highly significant (p less than 0.001) across doses of 15, 20, and 40 mg of intravenously administered cocaine. These findings are important in that they allow monitoring blood levels of cocaine after intravenous infusion in a non-invasive manner, and could form the basis for development of a non-invasive screen for active cocaine levels in saliva.

Cocaine↗

PubMedDate not supplied

Correlation of saliva cocaine levels with plasma levels and with pharmacologic effects after intravenous cocaine administration in human subjects.

The behavioral and physiologic effects of single, intravenous bolus doses of cocaine in 5 male human subjects were correlated with cocaine levels in saliva and blood. All measures were performed under double-blind conditions. Two test doses of cocaine (15 mg and 40 mg) and one placebo test dose were administered to each subject in a random, cross-over design. Each test day was separated by a minimum of 48 h. Cocaine levels in saliva and blood significantly (p less than or equal to 0.05) correlated with responses on self-rating scales for drug sensation (Feel Drug scale), psychotomimetic effects (LSD scale), and feelings of rush (Rush scale). Significant (p less than or equal to 0.01) correlations also were obtained with cocaine biofluid levels and pulse rate. The close relationship observed between cocaine saliva levels and cocaine-induced behavior and physiologic effects presents the opportunity for development of a new noninvasive method for detection of current cocaine use.

Adult↗

PubMedDate not supplied

The role of acetylator genotype on hepatic and extrahepatic acetylation, deacetylation, and sulfation of 2-aminofluorene, 2-acetylaminofluorene, and N-hydroxy-2-acetylaminofluorene in the inbred hamster.

In vitro rates of acetylation, deacetylation, and sulfation were measured with carcinogenic arylamine, arylamide, and arylhydroxamic acid substrates using enzyme preparations derived from inbred hamster tissues of known acetylator genotype. Homozygous rapid acetylators (Bio. 87.20), heterozygous acetylators (Bio. 87.20 X Bio. 82.72/H F1), and homozygous slow acetylators (Bio. 82.73/H) did not differ significantly with respect to paraoxon-resistant intermolecular N,N-transacetylation reactions from N-hydroxy-2-acetylaminofluorene to 4-aminoazobenzene in tissue cytosol. Similarly, they did not differ with respect to paraoxon-sensitive, microsomal N-hydroxy-2-acetylaminofluorene and 2-acetylaminofluorene deacetylase, and cytosolic N-hydroxy-2-acetylaminofluorene sulfotransferase activity. However, a gene dose-response relationship was observed in the same animals for cytosolic acetyl coenzyme A-dependent 2-aminofluorene N-acetyltransferase activity. Partial purification of liver cytosol yielded two paraoxon-resistant isozyme forms of acetyltransferase activity. The rates of one isozyme were acetylator genotype dependent (polymorphic), whereas the rates of the second isozyme appeared to be acetylator genotype independent (monomorphic). Acetyl coenzyme A-dependent 2-aminofluorene N-acetyltransferase activity was catalyzed at high rates by both isozymes, whereas transacetylation of 4-aminoazobenzene by various acyl donors (N-hydroxy-2-acetylaminofluorene, N-hydroxy-4-acetylaminobiphenyl, and acetyl coenzyme A) was catalyzed primarily (but not exclusively) by the monomorphic acetyltransferase isozyme. These results provide further information concerning the importance of acetylator genotype in the metabolism of carcinogenic arylamines and their metabolites.

2-Acetylaminofluorene↗