In vitro experiments on chloroquine and pyrimethamine absorption in the presence of antacid constituents or kaolin.

A study was made in vitro of the effect of five gastrointestinal medications on the absorption of chloroquine and pyrimethamine, the two most commonly used antimalarial agents in the Sudan. Activated dimethicone did not appreciably affect the absorption of either antimalarial drug. All other agents tested significantly decreased the absorption of both chloroquine and pyrimethamine. The decreases observed were as follows: calcium carbonate (-52.8 and -31.5%), a local remedy, gerdiga (-36.1 and -38.0%), kaolin (-46.5 and -49.9%) and magnesium trisilicate (-31.3 and -37.5%) for chloroquine and pyrimethamine respectively. The results indicate that concomitant therapy of these antimalarials with the implicated antacid and antidiarrhoeal agents will result in poor bioavailability of the antimalarials.

The effect of magnesium trisilicate and kaolin on the in vivo absorption of chloroquine.

An in vitro study indicated that certain antacids and adsorbents may decrease the oral availability of th two widely used antimalarial agents chloroquine and pyrimethamine. To determine if this data was applicable to the clinical (in vivo) situation, plasma levels of one of the antimalarial agents (chloroquine) were followed in six Negro--Arab volunteers both when given alone and when taken with separate doses of two of the implicated interactants (magnesium trisilicate and kaolin). This in vivo work confirmed the in vitro findings; chloroquine area under the plasma concentration-time curve data were decreased by both magnesium trisilicate (18.2%) and kaolin (28.6%). Similar results could be expected for pyrimethamine. It is suggested therefore, to avoid loss of drug, that the antimalarials should not be taken with gastrointestinal medications of this type or that their administration should be separated by at least 4 h to reduce the risk of them interacting in the gut, thus preventing drug adsorption to the antacids/adsorbents, and loss of systemic availability.