Isoniazid is a drug used for the treatment of both immediate and chronic tuberculosis. It is broken down by the liver through pathways including the NAT2 enzyme. NAT2 slow acetylators accumulate higher levels of isoniazid and are thereby at increased risk for liver damage, while rapid acetylators are at increased risk of treatment failure, relapse, and acquisition of resistance.
With standard (non-personalized) therapy for tuberculosis, individuals might receive a standard dose (5 mg/kg) of isoniazid irrespective of acetylator status. With PGx-guided therapy, slow metabolizers might receive lower INH doses (2.5 mg/kg), while rapid metabolizers could receive increased doses (7.5 mg/kg), and intermediate metabolizers would receive standard doses (5 mg/kg). PGx-guided therapy of this type is estimated to reduce adverse events, improve efficacy, and save costs.[PMID 31905381]