Enhancement of moxidectin bioavailability in lamb by a natural flavonoid: quercetin

Area of Science:

• Veterinary Pharmacology
• Drug Metabolism
• Pharmacokinetics

Background:

• Moxidectin is a key antiparasitic drug for livestock and companion animals.
• Its metabolism involves P-glycoprotein (P-gp) and cytochrome P450 3A.
• Understanding factors affecting moxidectin bioavailability is crucial for optimizing its use.

Purpose of the Study:

• To investigate the impact of P-gp interfering agents on moxidectin metabolism.
• To evaluate the effect of ivermectin, quercetin, and ketoconazole on moxidectin bioavailability in lambs.
• To identify natural compounds that can enhance moxidectin's pharmacokinetic profile.

Main Methods:

• In vitro study using cultured rat hepatocytes to assess 14C moxidectin metabolism over 72 hours.
• In vivo study involving co-administration of moxidectin with ivermectin, quercetin, or ketoconazole in lambs.
• Pharmacokinetic analysis of moxidectin plasma concentrations.

Main Results:

• Ivermectin and quercetin significantly increased 14C moxidectin quantity in rat hepatocytes.
• Ketoconazole also led to higher moxidectin concentrations in hepatocytes.
• In vivo, only quercetin significantly increased the area under the plasma concentration-time curve for moxidectin in lambs.

Conclusions:

• Quercetin effectively modulates moxidectin pharmacokinetics, enhancing its bioavailability in lambs.
• This natural agent presents a promising strategy for improving moxidectin efficacy.
• The findings support the use of quercetin in combination therapies for parasitic infections in animals.