Chloroquine pharmacokinetics in tissues of pyrogen treated rats and implications for chloroquine related pruritus.

The concentrations of chloroquine in the tissues and plasma of control and pyrogen treated Long Island rats were serially determined over 16 days. Significant alterations of pharmacokinetic parameters, a delayed completion of distribution with a biphasic pattern of uptake of chloroquine into peripheral organs (skin and skeletal musculature) and increased tissue uptake in visceral organs (heart, liver and kidneys) of pyrogen treated rats were found. It is suggested that the known hemodynamic changes in the febrile state produced these unusual pharmacokinetic changes in the peripheral tissues and may contribute significantly to the occurrence of pruritus and increased acute toxicity of chloroquine during a febrile illness. The uptake patterns of chloroquine into pyrogen treated rat skin and muscle strongly suggest the involvement of a blood flow-dependent process in the movement of the drug into the tissues.