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Drug solubility within intestinal fluids can limit the overall absorption, as described in the maximum absorbable dose equation. This can become evident in early clinical testing where a single ascending dose study is planned. This study is used to determine the pharmacokinetic profile of a drug following a series of ascending oral doses as well as to explore the pharmacodynamic effects of an increasing dose. It is used within the safety assessment of a drug. If the solubility limits the exposure then work is required to ensure that the formulation used within the ascending dose study achieves the appropriate exposure to ensure linear pharmacokinetics. This is shown in Figure 4.1.

Figure 4.1 Image showing plasma pharmacokinetics from a study in which an oral ranging from 80 to 1000 mg was administered. It can be seen that the solubility limitation is reached at 400 mg whereby further increases in dose do not show increased Cmax or AUC.