Chloroquine excretion following malaria prophylaxis.

Area of Science:

• Pharmacokinetics
• Drug metabolism
• Tropical medicine

Background:

• Chloroquine is a widely used antimalarial drug.
• Understanding its long-term excretion is crucial for managing potential toxicity and drug interactions.
• Previous studies have not fully characterized the prolonged elimination phase.

Purpose of the Study:

• To quantify the urinary excretion and plasma concentrations of chloroquine and its primary metabolite, desethyl-chloroquine, after a standard course of malaria prophylaxis.
• To determine the terminal elimination half-lives and mean residence times of chloroquine and desethyl-chloroquine.

Main Methods:

• Oral chloroquine (300 mg base) was administered once weekly for 10 weeks for malaria prophylaxis.
• Urinary excretion and plasma concentrations of chloroquine and desethyl-chloroquine were monitored for up to 395 and 70 days, respectively.
• A three-compartment model was used to analyze the urinary excretion data.

Main Results:

• Urinary excretion of chloroquine and desethyl-chloroquine was detectable for up to 395 days post-treatment.
• Plasma concentrations were measurable for up to 70 days.
• Terminal phase half-lives ranged from 45-55 days for chloroquine and 59-67 days for the metabolite.
• Mean residence times were approximately 20 days for chloroquine and 35 days for the metabolite.

Conclusions:

• Chloroquine and its metabolite exhibit prolonged elimination, with significant urinary excretion persisting for over a year.
• The terminal elimination phases, while long, appear to have less impact on the overall effective half-life compared to earlier phases.
• These findings have implications for understanding chloroquine's long-term pharmacokinetics and potential for accumulation.