Nonparametric Expectation Maximisation (NPEM) Population Pharmacokinetic Analysis of Caffeine Disposition from Sparse Data in Adult Caucasians

Abstract

Collectively, the results show that the NPEM method is suitable and relevant for large-scale epidemiological studies of population phenotyping for cancer susceptibility and for abnormal liver function by monitoring CYP1A2 activity based on sparse caffeine data.

Prediction of drug clearance in a smoking population: modeling the impact of variable cigarette consumption on the induction of CYP1A2

“…Fig. 2), andfold increases (Table 3) in caffeine clearance for heavy smokers and all smokers relative to nonsmokers were in good agreement with observed data reported by Terziivanov et al [28]. However, for light smokers, both parameters were over-predicted by 1.5-fold when compared with corresponding in vivo data (Table 3).…”

“…Despite the fact that the latter was lower than is accepted for that of a probe drug (fm CYP1A2 of 0.45 versus 0.9), the model was able to capture with reasonable accuracy, differences in the mean value of Fig. 2 Predicted (open bars) and observed (hatched bars) caffeine clearance and associated variability for nonsmokers, light smokers, and heavy smokers (Terziivanov et al [28]). Results are displayed as boxand-whisker plots where the bar represents the upper and lower quartiles, median, mean (squares), and 90% confidence interval (whiskers) of data from 10 replicate trials using a study design consistent with the original published reference oral clearance between smokers and non-smokers (130 versus 100 L/h).…”

“…Because of the logistical problems in recording accurate smoking histories of subjects recruited into drug studies, only a limited number of subjects could be assigned to the sub-categories, particularly those involving "light smokers." Therefore, with the exception of the study reported by Terziivanov et al [28] subjects were categorized as nonsmokers or smokers.…”

“…A second dataset (Terziivanov et al [28]), including 20 nonsmokers and 14 smokers, was used to validate the smoking model. Because of the small number of smokers in this study, it was not feasible to stratify the smokers into the same daily cigarette consumption groups as shown in Table 1.…”

Comparative Pharmacokinetics and Metabolisms of Caffeine in Sheep Breeds

“…It has been determined that there are high correlations between plasma MRs determined at specific sampling times (2 and 12 hr) after CF administration and CF clearance [16,24,[28][29][30][31]34]. In the present study, as there were high correlation bet ween plasma (TB+PX+TP/CF) MR ratios calculated at 7 hr after CF administration and the Cl T of CF, it was concluded that this ratio determined at a single sampling time point can be used instead of CF clearance, which requires multiple samples.…”