Residual chloroquine and metabolites in man as a sequel of previous chloroquine medications: a urinary excretion study and its significance.

In malaria-endemic areas like Nigeria, chloroquine is used frequently and extensively in the management of attacks. In this investigation urine samples of six different adult subjects showed a significantly wide range of excretion of total chloroquine and metabolites (10.01 to 0.021 mg) in 12 h due to residual levels of the drug in the subjects as a function of time of last medication with the drug. Two subjects representing extreme users of the drug--a naive subject and a frequent user--were given 300 mg of chloroquine each and the excretion rate profile monitored for 24 h. The first-time user of chloroquine showed a typical cumulative excretion pattern with total excretion of 16 mg while the frequent user showed a bimodal cumulative excretion curve with the second phase tending to a higher plateau effect and a total excretion of 21 mg in 24 h. These different levels of total excretion could be attributed to the influence of protein binding and tissue accumulation of the drug in the frequent user, and a second-phase excretion related to release of some bound chloroquine and metabolites. These effects are considered in relation to accumulation of chloroquine in the body resulting from frequent medication with the drug. Information regarding the time of last medication, and residual levels of chloroquine and metabolites is necessary for instituting the appropriate therapeutic regimen. The assay techniques involving single selective solvent extraction, thin-layer chromatography and spectrophotometric measurements, have been found adequately quantitative, simple and quick for use in routine clinical laboratory investigation.