Pharmacokinetic profile noncompartmental pharmacokinetics

In pharmaceutical research and drug development, noncompartmental analysis is normally the first and standard approach used to analyze pharmacokinetic data. The aim is to characterize the disposition of the drug in each individual, based on available concentration-time data. The assessment of pharmacokinetic parameters relies on a minimum set of assumptions, namely that drug elimination occurs exclusively from the sampling compartment, and that the drug follows linear pharmacokinetics that is, drug disposition is characterized by first-order processes (see Chapter 7). Calculations of pharmacokinetic parameters with this approach are usually based on statistical moments, namely the area under the concentration-time profile (area under the zero moment curve, AUC) and the area under the first moment curve (AUMC), as well as the terminal elimination rate constant (Xz) for extrapolation of AUC and AUMC beyond the measured data. Other pharmacokinetic parameters such as half-life (t1/2), clearance (CL), and volume of distribution (V) can then be derived. 

Pharmacokinetics After Oral and Intravenous Administration. For proper characterization of an inhalation drug, information on the systemic pharmacokinetic properties needs to be provided. One of the major challenges for such studies is to provide a suitable formulation for injection, especially because new drug candidates are often very lipophilic. The resulting parameters of such studies (systemic clearance, volume of distribution, half-life, mean residence time) can then easily be extracted from concentration-time profiles after IV administration and subsequent standard pharmacokinetic analysis by noncompartmental approaches. In addition, a detailed compartmental analysis based on concentration-time profiles will be useful in evaluating the systemic distribution processes in sufficient detail. This will be especially important if deconvolution procedures (see later) are included for the assessment of the pulmonary absorption profiles. 

Intravenous Drug Disposition. The estimation of primary pharmacokinetic parameters using noncompartmental analysis is based on statistical moment theory [45, 46]. The relationships dehned by this theory are valid under the assumption that the system is linear and time-invariant. For simplicity, we further assume that drug is irreversibly removed only from a single accessible pool (e.g., plasma space). Regardless of the route of administration, the temporal profile of plasma drug concentrations, Cp(t), can represent a statistical distribution curve. As such, the zeroth and first statistical moments (Mo and Mi) are defined as ... 

Various pharmacokinetic parameters such as CL, Vd, F%, MRT, and im can be determined using noncompartmental methods. These methods are based on the empirical determination of AUC and AUMC described above. Unlike compartmental models (see below), these calculation methods can be applied to any other models, provided that the drug follows linear pharmacokinetics. However, a limitation of the noncompartmental method is that it cannot be used for the simulation n of different plasma concentration-time profiles when there are alterations in dosing regimen or when multiple dosing regimens are used. 

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