Pharmacokinetics sample analysis

Sample throughput — Sample analysis (including analytical repeats and reassays for pharmacokinetic purposes) was performed between 25 August 2004 and 26 October 2004. Analytical results from 6875 samples were finalized during this period. 

Shou, W. Z. Naidong, W. Postcolumn infusion study of the dosing vehicle effect in the liquid chromatography/tandem mass spectrometric analysis of discovery pharmacokinetic samples. Rapid Commun Mass Spectrom 2003, 17, 589-597. 

Sample analysis requires specific techniques, such as fluorescence polarization immunoassay (FPIA) and high-performance liquid chromatography (HPLC). These techniques are not always available in the pharmacy and so sample analysis is not always done in Spanish hospital pharmacy services but in laboratories. However, it is a pharmacist who interprets results, makes recommendations, and follows up on patients, all as part of clinical activities to pursue better patient care. In all hospitals with such a pharmaceutical service, doctors and other members of the health team welcome the contribution of pharmacists, with their pharmacokinetic knowledge, to the rational use of drugs. 

Shou, W.Z. Naidong, W. Post-Column Infusion Study of the Dosing Vehicle Effect in the Liquid Chromatography/Tandem Mass Spectrometric Analysis of Discovery Pharmacokinetic Samples, Rapid Commun. Mass Spectrom. 17, 589-597 (2003). 

Villa, J.S. Cass, R.T. Carr, D.E. Adams, S.M. Shaw, J.P Schmidt Jr., D.E. Increasing the Efficiency of Pharmacokinetic Sample Procurement, Preparation and Analysis by Liquid Chromatography/Tandem Mass Spectrometry, Rapid Commun. Mass Spectrom. 18(10), 1066-1072 (2004). 

Recording details of the studies, including the models used and associated parameter values reported, is an obvious starting place. Additional details include the chemical analysis method, the pharmacokinetic analysis method, the studied population (specifically subpopulations), number of healthy volunteers or patients, number of pharmacokinetic samples per patient, the dose, the formulation, and the route of administration. If one publication includes several groups of patients (or the same patient received two different formulations/concomitant medications), then each cohort may need to be treated as a repeated measure of the same study or within the same study, which may be indexed according to a study or patient covariate. 

Table 1.10 presents a sample table of contents for a modeling report used in support of a pharmacokinetic-pharmacodynamic analysis. The order of the report follows that of a scientific paper introduction, methods, results, and discussion. Within each section, the relevant aspects related to the model are presented. For example, within the discussion section, how plausible the model is,... 

In cases where the study sponsor or pharmacokineticist5 assumes responsibility for selecting samples for repeat analysis, the bioanalytical laboratory should require and maintain written documentation of the request in the study file. The written documentation should identify the samples selected by the sponsor or pharmacokineticist, along with the basis for the selection. Ideally, the selection criteria used by the sponsor or pharmacokineticist should be provided to the bioanalytical laboratory in advance of sample analysis and maintained in the study file. Similarly, if the sponsor or pharmacokineticist assumes responsibility for determining the value reported for pharmacokinetic calculations, the SOP followed by the sponsor or pharmacokineticist in this regard should also be provided to the bioanalytical laboratory to facilitate a complete record for reconstructing the study conduct. 

Samples of blood and excreta are taken for laboratory analysis. It is expected that, at the end of this phase, you will have a preliminary estimate of the maximum dose that may be safely tolerated in humans, and also a basic profile of the drug s pharmacokinetic behaviour. Depending on the availability of appropriate analytical indicators, pharmacodynamic and indicative efficacy data may also be generated. The data acquired must be carefully analysed and assessed so that, based on the findings, appropriate Phase II trials can be planned. 

Analysis of most (perhaps 65%) pharmacokinetic data from clinical trials starts and stops with noncompartmental analysis (NCA). NCA usually includes calculating the area under the curve (AUC) of concentration versus time, or under the first-moment curve (AUMC, from a graph of concentration multiplied by time versus time). Calculation of AUC and AUMC facilitates simple calculations for some standard pharmacokinetic parameters and collapses measurements made at several sampling times into a single number representing exposure. The approach makes few assumptions, has few parameters, and allows fairly rigorous statistical description of exposure and how it is affected by dose. An exposure response model may be created. With respect to descriptive dimensions these dose-exposure and exposure-response models... 

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