Population pharmacokinetics documentation

The Guidance for Industry Population Pharmacokinetics clearly states that any type of population pharmacokinetic (PK) analysis should be defined in a protocol (7). The justification for this is that objectivity should be retained through prespecification of all procedures and methodologies that will be used. In the pharmaceutical industry this protocol usually takes the form of a plan for the analysis, either produced as part of the clinical trial protocol or as a separate document. 

Create internal repository of complete population pharmacokinetic efforts (code, model development chronology, documentation, etc.)... 

In addition, the CPMP adopted in May 2002 a concept paper (CPMP/EWP/968/02) on a proposal to develop a CPMP Points to Consider document on the evaluation of the pharmacokinetics of medicinal products in the paediatric population. 

Carbamazepine (CBZ) and divalproex sodium (DVP) are the most common anticonvulsant agents prescribed for adult BD (Bowden et ah, 1994) Post et ah, 1998b) and pediatric epileptic disorders (Trimble, 1990 Dunn et al., 1998). As a consequence of their documented efficacy in these populations, their use has been extended to pediatric behavioral and mood disorders (Biederman et ah, 1998). We review here their mechanisms of action, pharmacokinetics, side effects, and pediatric uses. The multiple cytochrome P450 (CYB)-mediated potential drug interactions of CBZ and DVP are not covered in detail in this chapter. For a comprehensive review of this subjects the reader is referred to a recent publication by Flockhart and Oesterheld (2000). 

The two factors responsible for increasing risks of ADRs in children are pharmacokinetic changes and dose delivery issues. Age-related differences in pharmacokinetics in children are documented. However, the data on both efficacy and safety are often limited or not studied at all in this population. Thus, it is unclear whether an increased risk for ADRs exists in this group. However, there is a potential risk for increased ADRs if appropriate considerations are not taken into account in view of pharmacokinetic changes. ... 

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