DIFFERENTIAL UPTAKE OF CHLOROQUINE BY HUMAN KERATINOCYTES AND MELANOCYTES IN CULTURE

The antimalarial drug chloroquine has a high affinity for melanin and accumulates in melanin-rich compartments such as those of the eye, Chl oroquine is also deposited in cutaneous tissue, but whether the drug d istribution is restricted to melanin-producing cells of the skin is no t known, In the present study, the uptake of chloroquine by normal hum an epidermal keratinocytes was compared with that by melanocytes, Sele ctively cultivated cells were incubated at drug concentrations ranging between 0 and 10 000 ng/ml for periods of up to 48 h, Chloroquine was quantified in cells and medium using high performance liquid chromato graphy and fluorometric detection, In both types of cells there was a rapid uptake of chloroquine within the first 2 h, followed by a slower uptake for 2-6 h until a steady-state condition was reached, Dose dep endency was linear, with no sign of saturation, and approximately ten times higher drug concentrations were attained in melanocytes as compa red with keratinocytes, No formation of desethylchloroquine, the major systemic metabolite, was detected in either cell type. The observed a ffinity of chloroquine for normal epidermal melanocytes in vitro sugge sts that the density and melanogenic activity of skin pigment cells ma y influence the cutaneous drug disposition of chloroquine.