Pharmacokinetics circulating blood

Pharmacokinetis were evaluated in 15 pts. Mean plasma concentrations oftotal-DXR, free-DXR, encapsulated-DXR at level 4 was shown in Fig 2. Table 4 shows the mean pharmacokinetic parameters of total-DXR, free-DXR-and metabolites in plasma at level 1 to level 4. The plasma concentration of total-DXR at each level reached Cmax at the end of infusion. The plasma concentration profiles of total-DXR at level 1 to 3 showed biphasic elimination pattern but showed monophasic elimination pattern at level 4, because one subject at level 4 showed monophasic elimination pattern with a long half-life. CL, Vdss, and MRT of total-DXR were almost the same among dose levels. T1/2A.Z of total-DXR was prolonged by dose escalation, because the concentration of terminal phase was detected as dose increased (Table 4). Most oftotal-DXR could exist in circulating blood as an encapsulated form, because plasma concentration of... 

Figure 5,4 Pharmacokinetics. The absorption distribution and fate of drugs in the body. Routes of administration are shown on the left, excretion in the urine and faeces on the right. Drugs taken orally are absorbed from the stomach and intestine and must first pass through the portal circulation and liver where they may be metabolised. In the plasma much drug is bound to protein and only that which is free can pass through the capillaries and into tissue and organs. To cross the blood brain barrier, however, drugs have to be in an unionised lipid-soluble (lipophilic) form. This is also essential for the absorption of drugs from the intestine and their reabsorption in the kidney tubule. See text for further details...

FIG. 1 Schematic presentation of pharmacokinetics in the human body. The arrows indicate possible routes of drug adminsitration and the direction of the blood flow in the circulation. 

Figure 3 Possible blood circulation connections in a physiologically based pharmacokinetic model. (A) Venous return incorporated into lung mass balance equation (B) separate venous blood compartment. See text for definition of symbols.

Insulin, whatever its source, may be formulated in a number of ways, generally in order to alter its pharmacokinetic profile. Fast (short)-acting insulins are those preparations that yield an elevated blood insulin concentration relatively quickly after their administration (which is usually by s.c. or, less commonly, by i.m. injection). Slow-acting insulins, on the other hand, enter the circulation... 

Once a chemical is in systemic circulation, the next concern is how rapidly it is cleared from the body. Under the assumption of steady-state exposure, the clearance rate drives the steady-state concentration in the blood and other tissues, which in turn will help determine what types of specific molecular activity can be expected. Chemicals are processed through the liver, where a variety of biotransformation reactions occur, for instance, making the chemical more water soluble or tagging it for active transport. The chemical can then be actively or passively partitioned for excretion based largely on the physicochemical properties of the parent compound and the resulting metabolites. Whole animal pharmacokinetic studies can be carried out to determine partitioning, metabolic fate, and routes and extent of excretion, but these studies are extremely laborious and expensive, and are often difficult to extrapolate to humans. To complement these studies, and in some cases to replace them, physiologically based pharmacokinetic (PBPK) models can be constructed [32, 33]. These are typically compartment-based models that are parameterized for particular... 

Fish possess a large number of unique features that differentiate them both structurally and functionally from other vertebrates. Many of these biological features, including the gills, blood circulation and blood characteristics, and hepatic, renal, and digestive functions, are critical to drug pharmacokinetics. 

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