Cocaine, norcocaine, ecgonine methylester and benzoylecgonine pharmacokinetics in the rat

Berend Mets, Jaime Diaz, Ed Soo, Subhash Jamdar

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

We have compared the pharmacokinetics of bolus dose cocaine administration with that of its three most important metabolites; norcocaine, ecgonine methylester, and benzoylecgonine and assessed whether kinetics are dose dependent at two equimolar doses equivalent to cocaine hydrochloride 2.5 and 5mg/kg respectively. Forty-nine male Sprague-Dawley rats were randomly divided into 8 groups to receive iv either high (14.7 umol/kg) (HI) or low (7.3 umol/kg) (LO) bolus doses of cocaine or one of its metabolites. Arterial blood samples for cocaine and metabolite analysis were taken repetitively over the next 3 h. Equimolar bolus doses of these congeners showed biexponential plasma concentration decay curves which were fitted to a two compartment model and subjected to noncompartmental analysis. The plasma concentration time profiles were significantly different for the HI and LO doses administered for each congener. The elimination half-lives of cocaine and norcocaine were similar (28-33 min), that for ecgonine methylester (60- 71min) was approximately twice this and for benzoylecgonine was 40-44 min. Cocaine clearance (155158 ml/kg/min) was found to be in the range found in other rat studies. Ecgonine methylester clearance and benzoylecgonine clearance were found to be one quarter and one eighth of this value respectively. The pharmacokinetic profile of these congeners was not dose dependent when the two doses administered were compared.

Original languageEnglish (US)
Pages (from-to)1317-1328
Number of pages12
JournalLife Sciences
Volume65
Issue number12
DOIs
StatePublished - Aug 13 1999

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Pharmacokinetics
Cocaine
Rats
Metabolites
Plasmas
Sprague Dawley Rats
norcocaine
ecgonine
benzoylecgonine
Blood
Kinetics

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Mets, Berend ; Diaz, Jaime ; Soo, Ed ; Jamdar, Subhash. / Cocaine, norcocaine, ecgonine methylester and benzoylecgonine pharmacokinetics in the rat. In: Life Sciences. 1999 ; Vol. 65, No. 12. pp. 1317-1328.
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Cocaine, norcocaine, ecgonine methylester and benzoylecgonine pharmacokinetics in the rat. / Mets, Berend; Diaz, Jaime; Soo, Ed; Jamdar, Subhash.

In: Life Sciences, Vol. 65, No. 12, 13.08.1999, p. 1317-1328.

Research output: Contribution to journalArticle

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