Pharmacokinetics of chloroquine: saliva and plasma levels relationship.

The use of saliva levels as an alternative to plasma levels in monitoring chloroquine therapy was studied in five healthy volunteers. Subjects took two (250 mg) tablets of chloroquine diphosphate (300 mg chloroquine base) with 200 ml of water. Saliva and blood samples were collected at intervals over 6 days. Plasma was separated from blood samples after centrifugation while saliva samples were centrifuged to remove mucoid sediments. Both the plasma and saliva samples were analysed for chloroquine by a combination of thin-layer chromatography and spectrophotometry. Regression analysis was used to determine the correlation between saliva and plasma chloroquine levels. A significant correlation (r = 0.97, p less than 0.05) was observed between saliva and plasma levels of chloroquine. The saliva: plasma concentrations ratio was found to be 0.53. From the saliva: plasma relationship, the extent of chloroquine binding to plasma proteins was estimated to be 47%. The Cmax and AUC0-6 day values obtained from saliva data was about half those from plasma, while the Tmax obtained from both fluids remained the same. The saliva clearance rate (Cls/F) of chloroquine was about twice the plasma clearance rate (Cl/F). (Cls/F: 0.46 +/- 0.051/day/kg; 0.27 +/- 0.021/day/kg). However, the predicted Cl/F (0.27 +/- 0.031/day/kg) from saliva data was in agreement with Cl/F from plasma data. This was also true of the volume of distribution. The collection of saliva for measuring chloroquine levels provides a painless, non-invasive alternative to plasma sampling, and it is useful in predicting chloroquine pharmacokinetics.