CYTOTOXICITY TESTING OF BETA-LACTAM ANTIBIOTICS, NONSTEROIDAL ANTIINFLAMMATORY DRUGS AND SULFONAMIDES IN PRIMARY HUMAN KERATINOCYTE CULTURES

We have studied the cytotoxity to human keratinocytes of three main cl asses of drugs known to induce cutaneous adverse reactions, namely bet a-lactam antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs) a nd sulfonamides, using the neutral red uptake as an endpoint. IC50 val ues were determined for 21 drugs, after 20 hr of exposure and compared with those obtained with rat hepatocytes. NSAIDs were found to be mor e cytotoxic than beta-lactam antibiotics to human keratinocytes. Large variations in IC50 values were obtained between molecules of a same c lass, as well as between keratinocyte cultures from different donors, especially for beta-lactam antibiotics. All NSAIDs and beta-lactam ant ibiotics tested were more cytotoxic to rat hepatocytes (1.6- to 27-fol d). Both cell types were only slightly sensitive to sulfonamides, if a t all.