Post-distributive phase

MPA usually reaches maximal concentrations within an hour of the time of oral administration of MME Distribution of the drug is rapid and essentially complete in most patients within 2 to 3 hours of administration. In whole blood, >99.9% of the drug is in the plasma compartment. MPAs clearance is affected by (1) glucuronidation, (2) enterohepatic circulation (EHC), and (3) the quantity of its free fraction. EHC is considered to be a significant contributor to the dose interval kinetics of MPA, especially the post-distribution phase of the concentration-time curve. The contribution of EHC to the MPA AUC is about 37%, ranging from 10% to 61%, based on the effect of concomitant administration of cholestyramine. The appearance of a secondary MPA concentration peak anywhere from 4 to 12 hours following the morning dose of MMF is believed to result from EHC. 

Figure 1.11 clearly shows the presence of three phases in the plasma concentration versus time data for a drug administered by an extravascular route. Three phases include absorption, distribution and post-distribution. Please note that in the figure, there is a clear and recognizable distinction between the distribution and post-distribution phases. Furthermore, the plasma concentration... 

Most drugs entering the systemic circulation require a finite time to distribute completely throughout the body. This is particularly obvious upon rapid intravenous administration of drugs. During this distributive phase, the drug concentration in plasma will decrease more rapidly than in the post-distributive phase. Whether or not such a distributive phase is apparent will depend on the frequency with which blood samples are collected. A distributive phase may last for few minutes, for hours or, very rarely, even for days. 

Equation for predicting plasma concentration during distribution and post- distribution phases. 

X for a two-compartment model drug, the mass of dmg present in the body in the post-distribution phase... 

Collection of blood samples for at least three half times of elimination and at a frequency that captures distribution phase, Cmax and 7max, all at identical times post-dose for each formulation being compared. 

Figure 10.69 Graphical representation of the distribution phase (rapidly declining concentration) and elimination phase (slowly declining concentration) during the post-infusion period for a two-compartment IV infusion model.

Fig 2.2.2. Immediate post-surgical phases - stroke. A 55-year-old woman 14 days status post orthotopic heart transplant for constrictive/restrictive cardiomyopathy developed an acute embolic occlusion of the right middle cerebral artery trunk. Head CT demonstrated a large infarct in that right middle cerebral artery distribution with compression of the ventricles and some midline shift... 

Chain-Growth Associative Thickeners. Preparation of hydrophobically modified, water-soluble polymer in aqueous media by a chain-growth mechanism presents a unique challenge in that the hydrophobically modified monomers are surface active and form micelles (50). Although the initiation and propagation occurs primarily in the aqueous phase, when the propagating radical enters the micelle the hydrophobically modified monomers then polymerize in blocks. In addition, the hydrophobically modified monomer possesses a different reactivity ratio (42) than the unmodified monomer, and the composition of the polymer chain therefore varies considerably with conversion (57). The most extensively studied monomer of this class has been acrylamide, but there have been others such as the modification of PVAlc. Pyridine (58) was one of the first chain-growth polymers to be hydrophobically modified. This modification is a post-polymerization alkylation reaction and produces a random distribution of hydrophobic units. 

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