Cumulative Subject kinetics

Sohn et al. [148] examined the kinetic variables of omeprazole and its two primary metabolites in plasma, 5-hydroxyomeprazole and omeprazole sulfone, and the excretion profile of its principal metabolite in urine, 5-hydroxyomeprazole, in eight extensive metabolizers and eight poor metabolizers. Each subject received a postoral dose of 20 mg of omeprazole as an enteric-coated formulation, and blood and urine samples were collected up to 24 h postdose. Omeprazole and its metabolites were measured by HPLC with UV detection. The mean omeprazole area under the concentration-time curve, elimination half-life, and apparent postoral clearance were significantly greater, longer, and lower, respectively, in the poor metabolizers than in the extensive metabolizers. The mean cumulative urinary excretion of 5-hydroxyomeprazole up to 24 h postdose was significantly less in the poor metabolizers than in the extensive metabolizers. 

The use of derivative methods avoids the need for approximations to the temperature integral (discussed above). Measurements are also not subject to cumulative errors and the often poorly-defined boundary conditions used for integration [74], Numerical differentiation of integral measurements normally produces data which require smoothing before further analysis. Derivative methods may be more sensitive in determining the kinetic model [88], but the smoothing required may lead to distortion [84],... 

---