Sampling drug distribution studies

Mathematical models allow for considerable data compression. Data that fill many notebooks and/or tables may be summarized by means of the few parameters of a well chosen model. Plasma concentration versus time data collected during a pharmacokinetic study in many patients may be summarized using a volume of distribution term and an elimination half-life. Other models may include more parameters, but there is always a considerable compression in the information required to describe the overall results of the study. An extensive drug stability study involving many samples stored at various elevated temperatures may be summarized as a single time for 10% decomposition at room temperature. Determination of appropriate models can be a very useful method of summarizing an experimental study. 

In addition to some early applications in bioanalysis, ambient ionization mass spectrometry has been used as an imaging tool to study drug distribution in tissue sections. Most of the work reported so far involved the use of DESI as the ambient ionization method. Compared to other mass spectrometry-based tissue imaging techniques such as MALDI and SIMS, DESI allows tissue samples to be analyzed under ambient conditions without sample preparation, which simplifies the procedure and prevents the redistribution of analytes during matrix deposition. A major drawback of DESI as an imaging tool is its relatively low spatial resolution (typically 250 pm) and therefore cannot be used for cellular or subcellular imaging. 

Clark et al. [136] studied the excretion, distribution, and metabolism of primaquine in rats. The drug was administered intravenously, intraperitoneally, and orally and blood samples were collected at various time intervals. Primaquine was metabolized by oxidative deamination to give 8-(3-carboxy-l-methylpropylamino)-6-methoxy quinoline. The plasma levels of both primaquine and its metabolites were determined by high performance liquid chromatography. 

Comparative studies on the bioavailability of three different tretinoin gel formulations showed that the dimensions of the sampling area may play a critical role in determining the extent of dermal drug uptake [33, 34], If, by lateral spreading, a substance is distributed over an area sufficiently larger than the sampling area, significant proportions of compound will not be recovered and hence permeability will be underestimated. 

The distribution and excretion of tritiated vincristine were studied by Castle and colleagues in rats and dogs (36). These investigators found that the drug was eliminated from the blood of both species in a biexponential manner, with half-lives of approximately 15 and 75 min. The persistence of low levels of radioactivity in the blood at late sampling times suggested that a third, very slow elimination phase contributes to the pharmacoki-... 

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