Doxorubicin pharmacokinetics in the rabbit

Area of Science:

• Pharmacology
• Toxicology
• Biochemistry

Background:

• Doxorubicin is a vital chemotherapeutic agent.
• Understanding its pharmacokinetics is crucial for optimizing treatment and minimizing toxicity.
• Metabolism and excretion pathways require detailed investigation.

Purpose of the Study:

• To quantify doxorubicin, doxorubicinol, and DOX aglycone in rabbit plasma, urine, and feces after intravenous administration.
• To characterize the pharmacokinetic profile and plasma protein binding of doxorubicin in rabbits.
• To evaluate the rabbit as a preclinical model for human doxorubicin pharmacokinetics.

Main Methods:

• Intravenous administration of doxorubicin (7.9 mg/kg) to New Zealand White rabbits.
• Quantification of doxorubicin and its metabolites using high-performance liquid chromatography and fluorometry.
• Analysis of plasma protein binding via ultracentrifugation and electrophoresis.

Main Results:

• Doxorubicin was the primary compound in rabbit plasma, with doxorubicinol and DOX aglycone in trace amounts.
• Plasma elimination followed a triphasic curve with half-lives of 2 min, 18 min, and 15 hours.
• Approximately 8.0% of the dose was excreted in urine, mainly as doxorubicinol and doxorubicin.

Conclusions:

• Doxorubicin exhibits dose-dependent pharmacokinetics in rabbits.
• The rabbit model demonstrates significant similarities to human pharmacokinetics and metabolism of doxorubicin.
• This validates the rabbit as a relevant preclinical model for anthracycline drug studies.