Two-compartment pharmacokinetic model

McCarley KD, Bunge AL (2000) Physiologically relevant two-compartment pharmacokinetic models for skin. J Pharm Sci 89 1212-1235. 

Wall et al.9 administered 1.3 pg/kg of 3H-PCP intravenously to human volunteers and collected blood samples for 72 h. Data from this study suggested a two-compartment pharmacokinetic model with a plasma half-life for PCP of 7 to 16 h. Domino et al.10 further analyzed the data from Wall et al. and developed a more complex three-compartment PK model. The reported half-lives for... 

Fig. 3.11 Schematic depiction of the simple two-compartment pharmacokinetic model with an input, transport between two compartments, and elimination from the central compartment.

Plasma concentration/time profiles after intravenous dosing were analyzed in terms of a two-compartment pharmacokinetic model. 

Other approaches have been used for more complex models. These include curve stripping or the method of residuals,either manually or using a computer program such as CSTRIP and ESTRIF. These techniques can separate a multiexponential curve into its component parts for initial estimates. Other techniques include deconvolution methods specific to the one and two compartment pharmacokinetic models. The objective of the deconvolution method is to mathematically subtract the results obtained after IV administration from the oral or extravascular data. This results in information about the input or absorption process alone. More general methods have been presented by various researchers that do not rely on a particular compartmental model. ... 

Fig. 3.2 Analogue computer-generated curves showing the levels (as fraction of the intravenous dose) of benzylpenicillin in the central (serum) and peripheral (tissue) compartments of the two-compartment pharmacokinetic model and the cumulative amount excreted unchanged in the urine as a function of time. The curves are based on the first-order rate constants (k12, k21, kel) associated with the compartmental pharmacokinetic model. Note...

For drugs that are best described by a two-compartment pharmacokinetic model, the absorption-time profile can be determined by the Loo-Riegelman method (Loo and Riegelman 1968). However, this method requires administration of an IV bolus dose to determine the disposition pharmacokinetics. Therefore, this method does not provide any clear advantages compared to deconvolution. 

Figure 7.4 Predicted concentration profiles from a two-compartment model. Results from a two-compartment pharmacokinetic model with elimination only from the central compartment (compartment 1) with ti/2 — 60 min and distribution to a peripheral compartment (compartment 2) with ti/2 = 6 min. Equations 7-12 and 7-14 are both plotted, (a) Concentration after ingestion (b) concentration with slow absorption.

In another study, four male volunteers were exposed to 80 ppm of styrene in a chamber for 6 hours. Venous blood samples were collected during exposure and a nearly simultaneous set of 10 blood and mixed exhaled air samples were collected following exposure for up to 40 hours. Blood levels during exposure rose rapidly and reached an almost constant level by the end of the 6 hours. Following exposure, the results showed that styrene was cleared from the blood according to a linear two-compartment pharmacokinetic model, with half-life values of 0.58 and 13 hours, for the rapid and slow elimination phases, respectively. 

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