Permeability-surface area product

FIGURE 34-3 Positron emission tomography using 13NH3 showing increased brain ammonia uptake in a patient with liver cirrhosis and mild hepatic encephalopathy. CMRA, cerebral metabolic ratio for ammonia HE, hepatic encephalopathy PS, permeability/surface area product. (With permission from reference [9].)... 

Abraham [1] modeled the BBB penetration in terms of the permeability-surface area product, PS (in units of cm3 s 1 g 1), using the linear free energy... 

Figure 2.4. In vivo measurement of blood-brain barrier (BBB) permeability, (a) Internal carotid artery perfusion technique (i) in the rat. Other branches of the carotid artery are ligated or electrically coagulated (o, occipital artery p, pterygopalatine artery). The external carotid artery (e) is cannulated and the common carotid artery (c) ligated. Perfusion time may range from 15 s to 10 min, depending on the test substance. It is necessary to subtract the intravascular volume, Vo, from (apparent volume of distribution), to obtain true uptake values and this may be achieved by inclusion of a vascular marker in the perfusate, for example labelled albumin. Time-dependent analysis of results in estimates of the unidirectional brain influx constant Ki (pi min which is equivalent within certain constraints to the PS product. BBB permeability surface area product PS can be calculated from the increase in the apparent volume of distribution Vd over time. Capillary depletion, i.e. separation of the vascular elements from the homogenate by density centrifugation, can discriminate capillary uptake from transcytosis. (b) i.v. bolus kinetics. The PS product is calculated from the brain concentration at the sampling time, T, and the area under the plasma concentration-time curve, AUC.

AUC, area under curve of plasma concentration Av, avidin NLA, neutral avidin SA, streptavidin cHSA, cationized human serum albumin HIR MAb, human insulin receptor mAb PS product, permeability surface area product. 

Plasma clearance (Cl), blood-brain barrier permeability surface area product (PS) and accumulation as % injected dose detected in brain tissue (%ID tissue) at 1 h after administration. Results show free [ H]-daunomycin (Daunomycin), [ H]-daunomycin encapsulated in conventional liposomes (Liposomes), sterically stabilized liposomes (PEG-liposomes), immunoliposomes (29 0X26, where 29 designates the number of 0X26 mAb conjugated per liposome) and control immunoliposomes where the 0X26 mAb was replaced by a non-specific isotype control antibody (IgG2a). Values are means SEM of n = 3 experiments. 

This equation for the concentration profile in the capillary has two terms. The first term is a delta function 8 (t — z/v) that travels through the capillary at velocity v and decays in strength exponentially as it travels from the inlet to the outlet of the capillary. The decay is due to permeation out of the capillary thus the decay constant is proportional to the permeability-surface area product of the capillary wall. If PS = 0, then the impulse travels along the capillary and reaches the outlet at undiminished strength at time t = L/v. The second term in Equation (8.47) represents the concentration profile in the capillary that trails behind the impulse. 

FIGURE 30.3 Peritoneal permeability-surface area product or clearance versus body weight across four species for urea ( ) and inulin ( ). (Reproduced from Dedrick RL et al. ASAIO J 1982 5 1-8.)... 

Fig. 1. Relationship between molecular radius and permeability/surface area product for intact capillaries.

PSi Permeability surface area product for the influx across the sinusoidal membrane... 

PSJF is the total capillary permeability-surface area product divided by the total flow of solute-containing mother fluid. PS IF is the analogous ratio for the cell PS. Yr is the ratio of volume of distribution in region r to the plasma volume,... 

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