Disposition kinetics of d- and I-amphetamine following intravenous administration of racemic amphetamine to rats

A. Hutchaleelaha, J. Sukbuntherng, Hsiao-Hui Chow, Michael Mayersohn

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Amphetamine (AP), a chiral drug, displays stereoselective differences in biological action. The effect of stereochemistry on the disposition kinetics of the enantiomers has not been thoroughly studied. We examined the disposition kinetics of AP in rats using a sensitive precolumn derivatization HPLC method that can separate the enantiomers of AP and its metabolites. Male Sprague-Dawley rats were given a short intravenous infusion of racemic AP (15 mg/kg). The systemic and renal clearances, steady-state volume of distribution, and terminal half-life for I-AP were (mean ± SD), respectively: 65.6 ± 9.25 ml/min · kg; 15.4 ± 2.55 ml/min · kg; 4.33 ± 0.71 liters/kg; and 0.96 ± 0.13 hr. The corresponding values for d-AP were: 50.8 ± 6.88 ml/min · kg; 12.5 ± 2.02 ml/min · kg; 3.84 ± 0.55 liters/kg; and 1.12 ± 0.09 hr. There are statistically significant differences between the enantiomers in all pharmacokinetic parameters except half-life. About 40% of the I-AP dose was excreted in urine as I-p-hydroxyamphetamine and 24% as intact drug. The corresponding values for d-AP were 32% and 26%, respectively. p-Hydroxyamphetamine was primarily excreted into urine as the conjugated form. These data indicate stereoselective differences in the pharmacokinetics of the enantiomers of AP after administration of racemic drug in the rat.

Original languageEnglish (US)
Pages (from-to)406-411
Number of pages6
JournalDrug Metabolism and Disposition
Volume22
Issue number3
StatePublished - 1994

Fingerprint

Dextroamphetamine
Amphetamine
Intravenous Administration
Rats
Enantiomers
Kinetics
p-Hydroxyamphetamine
Pharmacokinetics
Half-Life
Urine
Pharmaceutical Preparations
Stereochemistry
Metabolites
Intravenous Infusions
Sprague Dawley Rats
High Pressure Liquid Chromatography
Kidney

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Disposition kinetics of d- and I-amphetamine following intravenous administration of racemic amphetamine to rats. / Hutchaleelaha, A.; Sukbuntherng, J.; Chow, Hsiao-Hui; Mayersohn, Michael.

In: Drug Metabolism and Disposition, Vol. 22, No. 3, 1994, p. 406-411.

Research output: Contribution to journalArticle

@article{3ac82642550d4b8e8dbfad424648c51b,
title = "Disposition kinetics of d- and I-amphetamine following intravenous administration of racemic amphetamine to rats",
abstract = "Amphetamine (AP), a chiral drug, displays stereoselective differences in biological action. The effect of stereochemistry on the disposition kinetics of the enantiomers has not been thoroughly studied. We examined the disposition kinetics of AP in rats using a sensitive precolumn derivatization HPLC method that can separate the enantiomers of AP and its metabolites. Male Sprague-Dawley rats were given a short intravenous infusion of racemic AP (15 mg/kg). The systemic and renal clearances, steady-state volume of distribution, and terminal half-life for I-AP were (mean ± SD), respectively: 65.6 ± 9.25 ml/min · kg; 15.4 ± 2.55 ml/min · kg; 4.33 ± 0.71 liters/kg; and 0.96 ± 0.13 hr. The corresponding values for d-AP were: 50.8 ± 6.88 ml/min · kg; 12.5 ± 2.02 ml/min · kg; 3.84 ± 0.55 liters/kg; and 1.12 ± 0.09 hr. There are statistically significant differences between the enantiomers in all pharmacokinetic parameters except half-life. About 40{\%} of the I-AP dose was excreted in urine as I-p-hydroxyamphetamine and 24{\%} as intact drug. The corresponding values for d-AP were 32{\%} and 26{\%}, respectively. p-Hydroxyamphetamine was primarily excreted into urine as the conjugated form. These data indicate stereoselective differences in the pharmacokinetics of the enantiomers of AP after administration of racemic drug in the rat.",
author = "A. Hutchaleelaha and J. Sukbuntherng and Hsiao-Hui Chow and Michael Mayersohn",
year = "1994",
language = "English (US)",
volume = "22",
pages = "406--411",
journal = "Drug Metabolism and Disposition",
issn = "0090-9556",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "3",

}

TY - JOUR

T1 - Disposition kinetics of d- and I-amphetamine following intravenous administration of racemic amphetamine to rats

AU - Hutchaleelaha, A.

AU - Sukbuntherng, J.

AU - Chow, Hsiao-Hui

AU - Mayersohn, Michael

PY - 1994

Y1 - 1994

N2 - Amphetamine (AP), a chiral drug, displays stereoselective differences in biological action. The effect of stereochemistry on the disposition kinetics of the enantiomers has not been thoroughly studied. We examined the disposition kinetics of AP in rats using a sensitive precolumn derivatization HPLC method that can separate the enantiomers of AP and its metabolites. Male Sprague-Dawley rats were given a short intravenous infusion of racemic AP (15 mg/kg). The systemic and renal clearances, steady-state volume of distribution, and terminal half-life for I-AP were (mean ± SD), respectively: 65.6 ± 9.25 ml/min · kg; 15.4 ± 2.55 ml/min · kg; 4.33 ± 0.71 liters/kg; and 0.96 ± 0.13 hr. The corresponding values for d-AP were: 50.8 ± 6.88 ml/min · kg; 12.5 ± 2.02 ml/min · kg; 3.84 ± 0.55 liters/kg; and 1.12 ± 0.09 hr. There are statistically significant differences between the enantiomers in all pharmacokinetic parameters except half-life. About 40% of the I-AP dose was excreted in urine as I-p-hydroxyamphetamine and 24% as intact drug. The corresponding values for d-AP were 32% and 26%, respectively. p-Hydroxyamphetamine was primarily excreted into urine as the conjugated form. These data indicate stereoselective differences in the pharmacokinetics of the enantiomers of AP after administration of racemic drug in the rat.

AB - Amphetamine (AP), a chiral drug, displays stereoselective differences in biological action. The effect of stereochemistry on the disposition kinetics of the enantiomers has not been thoroughly studied. We examined the disposition kinetics of AP in rats using a sensitive precolumn derivatization HPLC method that can separate the enantiomers of AP and its metabolites. Male Sprague-Dawley rats were given a short intravenous infusion of racemic AP (15 mg/kg). The systemic and renal clearances, steady-state volume of distribution, and terminal half-life for I-AP were (mean ± SD), respectively: 65.6 ± 9.25 ml/min · kg; 15.4 ± 2.55 ml/min · kg; 4.33 ± 0.71 liters/kg; and 0.96 ± 0.13 hr. The corresponding values for d-AP were: 50.8 ± 6.88 ml/min · kg; 12.5 ± 2.02 ml/min · kg; 3.84 ± 0.55 liters/kg; and 1.12 ± 0.09 hr. There are statistically significant differences between the enantiomers in all pharmacokinetic parameters except half-life. About 40% of the I-AP dose was excreted in urine as I-p-hydroxyamphetamine and 24% as intact drug. The corresponding values for d-AP were 32% and 26%, respectively. p-Hydroxyamphetamine was primarily excreted into urine as the conjugated form. These data indicate stereoselective differences in the pharmacokinetics of the enantiomers of AP after administration of racemic drug in the rat.

UR - http://www.scopus.com/inward/record.url?scp=0028239436&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028239436&partnerID=8YFLogxK

M3 - Article

C2 - 8070317

AN - SCOPUS:0028239436

VL - 22

SP - 406

EP - 411

JO - Drug Metabolism and Disposition

JF - Drug Metabolism and Disposition

SN - 0090-9556

IS - 3

ER -