Diffusion drug distribution

Kretsos K, Kasting GB, Nitsche JM (2004) Distributed diffusion-clearance model for transient drug distribution within the skin. J Pharm Sci 93 2820-2835. 

DIFFUSION OF LIGAND TO RECEPTOR Drug clearance, dosage, PHARMACOKINETICS Drug distribution kinetics, PHARMACOKINETICS Drug excretion rates,... 

Drug Distribution. After administration, a drug may be distributed either generally or selectively in the body. The distribution pattern depends on many factors, including the pattern and time-course of blood (low, diffusion of drugs into tissues, binding of drugs to plasma proteins and cellular compartments, and elimination kinetics and mechanisms. 

Figure 2.8. Non-ionic diffusion in drug distribution, a Stmc-tuies of acetylcholine and of its two antagonists hexamethoninm and mecamylamine. Diffusion is facile in the non-ionic form (bottom left), whereas receptor binding requires the positive charge of the protonated state, b Acetylsalicylicacidisprotonat-ed in the acidic milieu of the stomach (left) and then enters the ep-ithehal cells by non-ionic diffusion. Deprotonation at the higher intracellnlarpH leads to accumulation inside the cells.

Two primary mechanisms of vitreal drug distribution and elimination are (i) diffusion from the lens region toward the retina with elimination via the retina-choroid-sclera and (ii) anterior diffusion with elimination via the hyaloid membrane and posterior chamber (18). Distribution to the retina from an intravitreal injection site is relatively slow, considering juxtaposition of the vitreous and retina, with the time for maximum drug concentration (tmax) in retina typically achieved at 4 to 12 hours, and reflects the inefficiency of diffusion over the distances encountered within the vitreous body. For example, ranibizumab, an ocular specific monoclonal VEGF antibody, distributes to the retina with of 6 to 24 hours. While relatively rapid therapeutically, this is slow compared with the rate of redistribution in stirred compartments. (249). 

Attempts were made to fit the in vivo serum concentration results to pharmacokinetic models based on revised diffusion-model equations for the uncoated and coated valve-rim Inserts. To couple the in vitro diffusion equations to an in vivo simulation, a classical one-compartment model of drug distribution was employed. The mean apparent volume of distribution, = 5.63 liters, and the first order eliminating constant, K = 0.695/hr, for gentamicin were determined in the intravenous fnjection-clearance studies. 

Friedrich S, Saville B, Cheng YL. Drug distribution in the vitreous humor of the human eye the effects of aphakia and changes in retinal permeability and vitreous diffusivity. J Ocul Pharmacol Ther 1997 13 445-459. 

Drug distribution in such sites or compartments is a complex process that depends on the systemic circulation concentration and subsequent passage across single cell endothelial or epithelial membranes with specialized physical and molecular barrier functionality. For certain orally administered AIDS medications (e.g., zidovudine and didanosine), oral absorption is limited because of poor absorption from the G1 tract, enzymatic biotransformation in the intestinal epithelium, or first-pass effects (Sinko et al., 1995, 1997). For other AIDS drugs (e.g., protease inhibitors), oral absorption may be complete however, drug distribution into the brain is limited by drug efflux proteins, which promiscuously interact and translocate lipophilic substrates back into blood as they diffuse into the BBB endothelium (Edwards et al., 2005 Kim et al., 1998). 

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