Cytotoxicity testing of beta-lactam antibiotics, non-steroidal anti-inflammatory drugs and sulfonamides in primary human keratinocyte cultures.

We have studied the cytotoxity to human keratinocytes of three main classes of drugs known to induce cutaneous adverse reactions, namely beta-lactam antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs) and sulfonamides, using the neutral red uptake as an endpoint. IC(50) values were determined for 21 drugs, after 20 hr of exposure and compared with those obtained with rat hepatocytes. NSAIDs were found to be more cytotoxic than beta-lactum antibiotics to human keratinocytes. Large variations in IC(50) values were obtained between molecules of a same class, as well as between keratinocyte cultures from different donors, especially for beta-lactum antibiotics. All NSAIDs and beta-lactam antibiotics tested were more cytotoxic to rat hepatocytes (1.6- to 27-fold). Both cell types were only slightly sensitive to sulfonamides, if at all.