Major and Minor Metabolites of Cocaine in Human Plasma following Controlled Subcutaneous Cocaine Administration

Kolbrich, Erin A.; Barnes, Allan J.; Gorelick, David A.; Boyd, Susan J.; Cone, Edward J.; Huestis, Marilyn A.

doi:10.1093/jat/30.8.501

Cited by 93 publications

(89 citation statements)

References 33 publications

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“…The authors also determined a fraction excreted of 10.8% of unidentified metabolites in urine, to which the later described metabolites can account for, namely p-and m-hydroxycocaine, p-and m-hydroxybenzoylecgonine, norcocaine, N-hydroxynorcocaine, norcocaine nitroxide and norcocaine nitrosonium ion (Kolbrich et al, 2006). 5.5% of COC dose was also determined to be excreted in feces.…”

Section: Sewage Back Calculations 261 Cocainementioning

confidence: 99%

Analysis of cocaine and nicotine metabolites in wastewater by liquid chromatography–tandem mass spectrometry. Cross abuse index patterns on a major community

Lopes

Silva

Bronze

et al. 2014

Science of The Total Environment

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HIGHLIGHTSCross abuse index patterns on licit and illicit drugs by means of sewage assessment Data about cocaine and nicotine consumption from a Portuguese population Co-evaluation of cocaine abuse estimates based on local drug purity levels ABSTRACT A method based on sample preparation by solid phase extraction and analysis by liquid chromatography and mass spectrometry was validated and used for simultaneous analysis of cocaine, benzoylecgonine and cotinine in samples collected at the major wastewater treatment plant in the city of Lisbon. The aim was to estimate the consumption of both cocaine and nicotine in this community and establish an index involving both drugs supported by the relevance of nicotine as a significant anthropogenic marker. The study was made on two different week days during a month in order to evaluate patterns of consumption outside weekends. Cocaine and nicotine ingestion levels were backcalculated and expressed as mass of pure drugs consumed per day and per 1000 inhabitants (mean: 0.604 g and 5.860 g respectively). Cocaine was also expressed on the basis of local drug purity levels (33.7%) with a corresponding increase on dose assessments, and community drug abuse profiles. The authors sustain that this approach should always be included in drug studies of this kind allowing a better drug abuse assessment. No significant different patterns of consumption were obtained during the working days studied with the exception of one case coincident with a national holiday that showed an increased typical profile found on other non-working day studies, namely weekends. A fairly significant relationship was found between nicotine and cocaine consumption that should be further evaluated in future studies. Pharmacokinetic considerations were made and proposed for cocaine assessment based on the impact on back calculations after common simultaneous consumption of cocaine and ethanol.

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Section: Sewage Back Calculations 261 Cocainementioning

confidence: 99%

Analysis of cocaine and nicotine metabolites in wastewater by liquid chromatography–tandem mass spectrometry. Cross abuse index patterns on a major community

Lopes

Silva

Bronze

et al. 2014

Science of The Total Environment

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“…Since its metabolism is dominated by hydrolytic ester cleavage, excreted metabolites consist mainly of benzoylecgonine (BEG) with lesser amounts of others like ecgonine methyl ester and ecgonine. Other minor cocaine metabolites are norcocaine (NCOC), p‐hydroxycocaine, m‐hydroxycocaine, p‐hydroxybenzoylecgonine, and m‐hydroxybenzoylecgonine 4, 5. COC is often taken with ethanol producing cocaethylene (CE), a psychoactive COC homologue 3…”

Section: Introductionmentioning

confidence: 99%

Norcocaine and cocaethylene distribution patterns in hair samples from light, moderate, and heavy cocaine users

Gambelunghe

Rossi

Aroni

et al. 2015

Drug Testing and Analysis

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Even though hair analysis often seems to be the best choice for retrospective monitoring of cocaine intake, differentiating between incorporated cocaine and external contamination is widely debated. In this study we report results obtained in 90 hair samples from addicts. All samples were analyzed for cocaine, benzoylecgonine, norcocaine, cocaethylene, and tropococaine by gas chromatography‐mass spectrometry (GC‐MS) techniques coupled with direct immersion solid‐phase micro‐extraction. Cocaine concentrations were stratified into three classes of usage: light (0.5–3 ng/mg), moderate (3.1–10 ng/mg) and heavy (10.1–40 ng/mg). The Substance Abuse and Mental Health Services Administration cut‐off criteria for establishing active cocaine use were applied to the results. For all samples criteria were cocaine levels above 0.5 ng/mg (ranging from 1.63 to 39.29 ng/mg, mean 9.49 ng/mg), benzoylecgonine concentrations ≥ 0.05 ng/mg (ranging from 0.19 to 5.77 ng/mg, mean 1.40), and benzoylecgonine to cocaine % ratio ≥5% (from 6.43 to 26.09%). Norcocaine was present in 58.9% of samples (concentration range: 0.22–3.14 ng/mg) and was strongly predictive only of heavy cocaine use (sensitivity 100% for cocaine concentrations above 9.58 ng/mg). Twenty hair samples from moderate and heavy users tested positive for cocaethylene (concentration range: 0.22–1.98 ng/mg, mean 0.73 ng/mg). This study on hair samples with no chance of false positive cases highlights the very limited applications of testing minor cocaine metabolites for definitive proof of active cocaine consumption. © 2015 The Authors. Drug Testing and Analysis Published by John Wiley & Sons, Ltd.

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“…Four outliers from the model (cocaine, gefitinib, telithromycin and verapamil) were highly under-predicted with FE > 4. The major metabolic pathways for cocaine are catalyzed by esterases in plasma and tissues, while CYP3A4 mediated demethylation is only a minor route (44). Gefitinib is mainly metabolized in the liver by cytochrome CYP3A4, CYP3A5 and CYP2D6.…”

Section: Qspkr Model For Drugs Substrates Of Cyp3a4 (Model 3)mentioning

confidence: 99%

Quantitative Structure – Pharmacokinetic Relationships for Plasma Clearance of Basic Drugs with Consideration of the Major Elimination Pathway

Zhivkova

2017

J Pharm Pharm Sci

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Purpose. The success of a new drug candidate is determined not only by its efficacy and safety, but also by proper pharmacokinetic behavior. The early prediction of pharmacokinetic parameters could save time and resources and accelerate drug development process. Plasma clearance (CL) is one of the key determinants of drug dosing regimen. The aim of the study is development of quantitative structure -pharmacokinetics relationships (QSPkRs) for the CL. Methods. A dataset consisted of 263 basic drugs, which chemical structures were described by 154 descriptors. Genetic algorithm, stepwise regression and multiple linear regression were used for variable selection and model development. Predictive ability of the models was assessed by internal and external validation. Results. A number of significant QSPkR models for the CL were derived with respect to the primary elimination pathway (renal excretion, metabolism, or CYP3A4 mediated biotransformation), as well for the unbound clearance (CL u ). The models were able to predict 52 -80% of the drugs from external validation sets within the 2-fold error of the experimental values with geometric mean fold error 1.57 -2.00. Conclusions. Plasma protein binding was the major restrictive factor for the CL of drugs, primarily cleared by metabolism. The clearance was favored by lipophilicity and several structural features like OH-groups, aromatic rings, large hydrophobic centers, aliphatic groups, connected with electro-negative atoms, and non-substituted aromatic Catoms. The presence of Cl-atoms and abundance of 6-member aromatic rings or fused rings had negative effect. The presence of ether O-atoms contributed negatively to the CL of both metabolism and renally excreted drugs, and urine excretion was favored by the presence of 3-valence N-atoms. These findings give insight on the main structural features governing plasma CL of basic drugs and could serve as a guide for lead optimization in the drug development process.

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Major and Minor Metabolites of Cocaine in Human Plasma following Controlled Subcutaneous Cocaine Administration

Cited by 93 publications

References 33 publications

Analysis of cocaine and nicotine metabolites in wastewater by liquid chromatography–tandem mass spectrometry. Cross abuse index patterns on a major community

Analysis of cocaine and nicotine metabolites in wastewater by liquid chromatography–tandem mass spectrometry. Cross abuse index patterns on a major community

Norcocaine and cocaethylene distribution patterns in hair samples from light, moderate, and heavy cocaine users

Quantitative Structure – Pharmacokinetic Relationships for Plasma Clearance of Basic Drugs with Consideration of the Major Elimination Pathway

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