In vitro binding of chloroquine to rat muscle preparations

Chloroquine (7-chloro-4-[[4-(diethylamino)-1-methylbutyl]amino]quinoline; CQ) accumulates in the insoluble fraction of rat muscle homogenates with an equilibrium distribution ratio of 7.8 L/kg. This is of a similar magnitude to muscle:plasma ratios observed in vivo. Uptake is approximately linear, even up to concentrations of free CQ greatly exceeding toxic plasma levels. Cell structural integrity is not essential for uptake, indicating that CQ is bound to tissue constituents and not trapped inside cells by an active process. At pH 7.4, binding of ionized CQ at anionic sites on tissue predominates over lipid partitioning of the un-ionized species. Binding to phospholipids is a major component of total muscle binding.