At the end of my medical training half a century ago, I asked my supervisor Georges Brouet, the eminent lung specialist who would go on to become Dean of the Paris Medical School, to allow me to write my dissertation on “Blood levels of active isoniazid and their practical relevance in the treatment of tuberculosis'. I defended this dissertation in 1961 and it caught the attention of Professor Etienne Bernard who awarded it a National Academy of Medicine prize.
The main practical findings were: the idea of fast and slow acetylators and of adjusting isoniazid dosage according to this metabolic status; relationships between neurotoxicological accidents caused by isoniazid and slow acetylator status; the consequences of impaired kidney and liver function on blood concentrations; and the need for dosage adjustment. It is interesting to see that, forty-five years later at a National Academy of Medicine meeting devoted to pharmacogenetics and pharmacogenomics presided over by the late, regretted Michel Bourel together with Raymond Ardaillou 1), a presentation by Michel Lhermitte et al. on genetic polymorphism and drugs addressed isoforms of N-acetyltransferase and the genotypic identification of fast and slow acetylators.
Advances in pharmacology and genetics have since shed light on an empirical observation that was originally based on simple clinical criteria and the results of bacteriologic tests on a reference strain conducted by Eugénie Bergogne-Berezin.