Effect of acute cocaine administration on the metabolism of antipyrine in vivo

Kloss, Michelle W.; Griffeth, Landis K.; Rosen, Gerald M.; Rauckman, Elmer J.

doi:10.1016/0006-2952(83)90165-x

Cited by 5 publications

(5 citation statements)

References 15 publications

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“…21 Cocaine has significant effects on hepatitic microsomal enzymes. 22,23 Phenytoin and rifampin may lower methadone serum levels by hepatitic enzyme enhancement, and cocaine may act in a similar manner. 24,25 Absorption of methadone from the gastrointestinal tract may also be impaired by cocaine.…”

Section: Discussionmentioning

confidence: 99%

Cocaine Abuse in Methadone Maintenance Patients Is Associated with Low Serum Methadone Concentrations

Tennant

Shannon²

1995

Journal of Addictive Diseases

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Cocaine abuse in methadone maintenance patients has emerged as a significant clinical problem. To determine if raising the daily methadone dosage is an effective way to eliminate cocaine abuse, 74 methadone maintenance patients maintained at daily dosages between 30 and 80 mg and who chronically abused cocaine were studied by a standard protocol. A total of 21 (28.4%) subjects ceased cocaine abuse when their methadone dosage was progressively raised to a maximal daily dose of 160 mg. Cocaine abuse appeared to accelerate elimination of methadone, since inadequate methadone serum concentrations (below 100 ng/ml) were found in 48 of 67 (71.6%) subjects tested 24 hours after a 100 mg oral methadone dose. Although cocaine abuse in methadone maintenance patients may respond to raising the daily methadone dosage, alternative treatments for cocaine abuse in methadone maintenance patients must be identified since cocaine abuse may lower serum methadone concentrations.

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Section: Discussionmentioning

confidence: 99%

Cocaine Abuse in Methadone Maintenance Patients Is Associated with Low Serum Methadone Concentrations

Tennant

Shannon²

1995

Journal of Addictive Diseases

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“…Enzymatic and nonenzymatic hydrolysis to benzoylecgonine accounts for an average of 45% of cocaine, while enzymatic hydrolysis to ecgonine methyl ester accounts for about 40% of cocaine metabolism, and microsomal oxidative metabolism of cocaine to norcocaine only accounts for a small percentage (1-3%) of the metabolized drug ( Jeffcoat et al, 1989;Benowitz, 1993;Gorelick, 1997;Scheidweiler et al, 2010;Yao et al, 2013). These cocaine metabolites and cocaine per se are potentially toxic to not only the CNS but also the heart, liver, and other organs (Kloss et al, 1983;Silva et al, 1991;Benowitz, 1993;Hollander, 1995;Restrepo et al, 2007). Therefore, vaccinemediated redistribution of administered cocaine and/or its metabolites represents a potential safety concern.…”

Section: Cocaine Metabolismmentioning

confidence: 99%

“…In addition to its profound effects on the brain and the heart, cocaine also has significant effects on peripheral organs, altering metabolism in the blood vessels, adrenal glands, and kidneys within minutes of cocaine administration (Benowitz, 1993;Blake et al, 1994;Mendelson et al, 2003). In these organs, butylcholinesterase and hydrolases enzymatically degrade the cocaine molecule (Barnett et al, 1981;Jeffcoat et al, 1989;Dean et al, 1992;Brzezinski et al, 1997;Gorelick, 1997), and these cocaine degradation products are potentially toxic in the organs in which they accumulate (Kloss et al, 1983;Silva et al, 1991;Lipton et al, 2000).…”

Section: Cocaine Metabolismmentioning

confidence: 99%

Fate of Systemically Administered Cocaine in Nonhuman Primates Treated with the dAd5GNE Anticocaine Vaccine

Hicks

Kaminsky

et al. 2014

Human Gene Therapy Clinical Development

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Cocaine use disorders are mediated by the cocaine blockade of the dopamine transporter in the central nervous system (CNS). On the basis of the concept that these effects could be obviated if cocaine were prevented from reaching its cognate receptors in the CNS, we have developed an anticocaine vaccine, dAd5GNE, based on a cocaine analog covalently linked to capsid proteins of an E1 -E3 -serotype 5 adenovirus. While the vaccine effectively blocks systemically administered cocaine from reaching the brain by mediating sequestration of the cocaine in the blood, the fact that cocaine also has significant peripheral effects raises concerns that vaccinationmediated redistribution could lead to adverse effects in the visceral organs. The distribution of systemically administered cocaine at a weight-adjusted typical human dose was evaluated along with cocaine metabolites in both dAd5GNE-vaccinated and control nonhuman primates. dAd5GNE sequestration of cocaine to the blood not only prevented cocaine access to the CNS, but also limited access of both the drug and its metabolites to other cocaine-sensitive organs. The levels of cocaine in the blood of vaccinated animals rapidly decreased, suggesting that while the antibody limits access of the drug and its active metabolites to the brain and sensitive organs of the periphery, it does not prolong drug levels in the blood compartment. Gross and histopathology of major organs found no vaccine-mediated untoward effects. These results build on our earlier measures of efficacy and demonstrate that the dAd5GNE vaccine-mediated redistribution of administered cocaine is not likely to impact the vaccine safety profile.

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Section: Cocaine Metabolismmentioning

confidence: 99%

Fate of Systemically Administered Cocaine in Nonhuman Primates Treated with the dAd5GNE Anti-cocaine Vaccine

Hicks¹,

Kaminsky²,

De³

et al. 2014

Human Gene Therapy Clinical Development

View full text Add to dashboard Cite

Cocaine use disorders are mediated by the cocaine blockade of the dopamine transporter in the central nervous system (CNS). Based on the concept that these effects could be obviated if cocaine were prevented from reaching its cognate receptors in the CNS, we have developed an anti-cocaine vaccine, dAd5GNE, based on a cocaine analog covalently linked to capsid proteins of an E1-E3- serotype 5 adenovirus. While the vaccine effectively blocks systemically administered cocaine from reaching the brain by mediating sequestration of the cocaine in the blood, the fact that cocaine also has significant peripheral effects raises concerns that vaccination-mediated redistribution could lead to adverse effects in the visceral organs. The distribution of systemically administered cocaine at a weight-adjusted typical human dose was evaluated along with cocaine metabolites in both dAd5GNE-vaccinated and control nonhuman primates. dAd5GNE sequestration of cocaine to the blood not only prevented cocaine access to the CNS, but also limited access of both the drug and its metabolites to other cocaine sensitive organs. The levels of cocaine in the blood of vaccinated animals rapidly decreased, suggesting that while the antibody limits access of the drug and its active metabolites to the brain and sensitive organs of the periphery, it does not prolong drug levels in the blood compartment. Gross and histopathology of major organs found no vaccine-mediated untoward effects. These results build on our earlier measures of efficacy and demonstrate that the dAd5GNE vaccine-mediated redistribution of administered cocaine is not likely to impact the vaccine safety profile.

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Effect of acute cocaine administration on the metabolism of antipyrine in vivo

Cited by 5 publications

References 15 publications

Cocaine Abuse in Methadone Maintenance Patients Is Associated with Low Serum Methadone Concentrations

Cocaine Abuse in Methadone Maintenance Patients Is Associated with Low Serum Methadone Concentrations

Fate of Systemically Administered Cocaine in Nonhuman Primates Treated with the dAd5GNE Anticocaine Vaccine

Fate of Systemically Administered Cocaine in Nonhuman Primates Treated with the dAd5GNE Anti-cocaine Vaccine

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