An improved formulation of chloroquine for intramuscular administration: absorption kinetics in rabbits

Intramuscular chloroquine is rapidly absorbed, even in severe falciparum malaria, and may cause potentially lethal hypotension. Less rapidly absorbed formulations should be safer. A chloroquine phosphate solution containing 2% methylcellulose 1500 released chloroquine 2.6 times more slowly than a commercial aqueous solution in an in-vitro absorption simulator. There was a log linear relationship between viscosity and release rate. The absorption pharmacokinetics of the more viscous chloroquine phosphate solution were then compared with those of a commercial solution after intramuscular injection to eight rabbits in an open cross over comparison. The rate of absorption was over three times slower with the viscous solution; median time to peak whole blood concentration with the commercial aqueous solution was 10 (range 5-20) min compared with 30 (range 10-60) min for the more viscous formulation (P less than 0.05). Peak whole blood concentrations were 66% (95% CI 50-82%) of those with the commercial preparation, but the acute bioavailability of the two solutions was similar. This simple new formulation may be safer than currently available chloroquine preparations and should now be evaluated in man.