Large theophylline requirements due to high theophylline clearance: verification by the antipyrine test

An asthmatic patient required very high doses of theophylline (2.88 g/day by intravenous infusion) to maintain an adequate serum theophylline concentration (12 micrograms/ml). His cigarette smoking and concurrent treatment with phenytoin were suspected to have produced hepatic microsomal enzyme induction, causing unusually high theophylline clearance. The intravenous antipyrine test demonstrated an unusually short half-life (5.5 h) and high clearance (95 ml/min) of antipyrine, consistent with induced clearance of antipyrine. Formation of the 4-hydroxy metabolite of antipyrine was disproportionately induced. Thus the antipyrine test can be of clinical value for documenting hepatic microsomal enzyme induction in patients with low steady-state theophylline concentrations despite high maintenance doses.