The disposition of free and liposomally encapsulated antimalarial primaquine in mice.

Plasma clearance, urinary excretion and tissue distribution of radiolabeled free (FPQ) and liposome-entrapped Primaquine (LPQ) in mice were monitored for 2 hr following intravenous administration. FPQ is eliminated very rapidly from the plasma and excreted predominantly in the urine, probably largely in a metabolized form. In decreasing order of magnitude, pronounced accumulation of label occurs in the liver, kidneys, lungs and skeletal muscle. Less than 1 per cent of the total initial dose is recovered in other tissues. Partial erythrocytic sequestration results in drug levels higher and more persistent in blood cells than in the plasma. Compared to the free drug form, Primaquine entrapped within negatively charged liposomes of the cholesterol-rich multilamellar type exhibits a prolonged plasmatic half-life and, within the observation period, excretion is 8-fold reduced. Liver accumulation of label is doubled, accounting for close to 50% of the injected dose; splenic uptake is tripled, while accumulation in the lungs, kidneys, heart and brain is drastically reduced. These differences in pharmacodynamic behaviour may explain why liposomal entrapment leads to diminished acute Primaquine toxicity.