Theophylline pharmacokinetics with concomitant steroid and gold therapy

Background: Theophylline has been used for several decades in the treatment of asthma. In recent years, however, with the appreciation of the importan ce of inflammation in the pathogenesis of asthma, new therapeutic approache s have arisen, including beta(2)-agonists, steroid and nonsteroidal anti-in flammatory drugs, such as gold salts. Objective: In the present work we studied the kinetic behaviour of theophyl line administered concomitantly with methylprednisolone (steroid compound) and auranofin (oral gold) in six adult female patients. Method: Drug concentration data for patients under routine care were collec ted. The kinetic analysis (Bayesian Approach) was done using two different commercial software packages, PKS (Abbott Diagnostics) and CAPCIL (SIMKIN I nc., courtesy of Dade-Behring). A one-compartment open model with first-ord er absorption (k(a) for PKS=0.5/h; k(a) for CAPCIL=0.3/h ) and first- order elimination. Default CL, t(1/2) and V-d values were used for each program was assumed. The measured and predicted theophylline concentrations were us ed to calculate percentage prediction errors defined as %PE=[(predicted con c. - measured conc.)/measured conc.] x 100. A linear regression analysis wa s also carried out for the observed concentrations and those predicted by e ach method (PKS vs. CAPCIL). Results: The predicted concentrations indicating persistently over-predicte d the observed theophylline serum levels (results expressed as median and i nterquartile range; %PE for PKS=58.1 [37.1-126.0]; %PE for CAPCIL=34.0 [12. 5-93.8]). The regression analysis confirmed the same tendency, showing an i ntercept significantly different from zero using both PKS and CAPCIL. Conclusion: The results suggest a possible interaction between theophylline and auranofin. Both PKS and CAPCIL failed to predict theophylline serum le vels based exclusively on population pharmacokinetic parameters. The lower observed concentrations than expected have obvious implications in practice . Periodic theophylline serum determinations are advisable until further st udies provide the necessary clarification about the kinetic profile of theo phylline in patients taking concomitant steroids and gold salts.