Lowering of theophylline clearance by isoniazid in slow and rapid acetylators

The effect of isoniazid (INH) pretreatment (400 mg daily for 2 weeks) on the elimination kinetics of theophylline (given intravenously as aminophylline equivalent to 151.2 mg theophylline) was investigated in 13 healthy male non-smokers. Amongst the 13 subjects studied, seven were rapid and six were slow acetylators. The mean clearance of theophylline was significantly lowered after INH (2.20 +/- 0.24 l h-1) (mean +/- s.e. mean) compared with the baseline value (2.80 +/- 0.24 l h-1). The volume of distribution at steady state was also lowered significantly after INH (0.42 +/- 0.01 l kg-1 vs 0.47 +/- 0.02 l kg-1). Consequently, there was no significant prolongation of theophylline half-life after INH (7.0 +/- 0.3 h vs 6.7 +/- 0.4 h control). The lowering of theophylline clearance by INH may be related to acetylator status since slow acetylators showed a greater interaction than rapid acetylators. However, this difference was not statistically significant.