Does sex affect theophylline Emax? A mixture model method

Abstract

Background The use of sex as a covariate to explain systematic differences in peak expiratory flow rate (PEFR) after treatment with theophylline has been studied using the likelihood ratio test (LRT) with NONMEM. Results were equivocal and depended on the NONMEM estimation method. Method A mixture model was used with NONMEM to estimate the probability that a model with an effect of sex on Emax (PEFR) was preferred over the same model without sex. The mixture model was also used to test an allometric function of body weight as a covariate on Emax. The evidence for a model including sex on Emax (Pr(sex)) was computed from the average of 1000 non-parametric bootstrap estimates of the mixing parameter. The odds favouring a model can be calculated from Pr(sex)/(1−Pr(sex)). The odds against the model is the inverse of this relationship. Results The odds favouring sex without weight were 4.7 while the odds against sex when allometric weight scaling was added into the model were 8.3. Conclusions Sex does not affect the Emax for theophylline. Any influence of sex can be explained by weight. Mixtures of models offer an alternative to the LRT for choosing among models. Clinical Pharmacology & Therapeutics (2005) 77, P93–P93; doi: 10.1016/j.clpt.2004.12.247