Variability inter-occasional

The statistical submodel characterizes the pharmacokinetic variability of the mAb and includes the influence of random - that is, not quantifiable or uncontrollable factors. If multiple doses of the antibody are administered, then three hierarchical components of random variability can be defined inter-individual variability inter-occasional variability and residual variability. Inter-individual variability quantifies the unexplained difference of the pharmacokinetic parameters between individuals. If data are available from different administrations to one patient, inter-occasional variability can be estimated as random variation of a pharmacokinetic parameter (for example, CL) between the different administration periods. For mAbs, this was first introduced in sibrotuzumab data analysis. In order to individualize therapy based on concentration measurements, it is a prerequisite that inter-occasional variability (variability within one patient at multiple administrations) is lower than inter-individual variability (variability between patients). Residual variability accounts for model misspecification, errors in documentation of the dosage regimen or blood sampling time points, assay variability, and other sources of error. 

Uncooked starch is occasionally sprayed between the plies on multi-ply paper and board mills as the simplest solution to the problem of poor or variable inter-ply bonding. 

The first report [138] on the stereoselective pharmacokinetics of tocainide measured plasma concentrations of tocainide enantiomers obtained occasionally from seven patients with life-threatening ventricular arrhythmia over a three-year period. Although large intra- and inter-individual variability was present, the plasma concentrations of the S enantiomer were always higher than those of R-tocainide [138]. Subsequent reports investigated the full pharmacokinetics of tocainide after the IV administration of the racemate to healthy volunteers [127,139] and anephric patients [127] and also after the oral administration of the individual enantiomers in healthy subjects [117] (Table 15). After the IV administration of the racemate, there is no stereoselectivity in the volume of distribution of the... 

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