Drug, distribution

Surface area The gastrointestinal tract and the small intestine in particular has a huge surface area, adapted for absorption because of this and despite the effects of pH most drugs are predominantly absorbed in the small intestine 

Gastric emptying and intestinal Drugs given with a meal take longer to be absorbed  

Blood flow The intestine has a good blood flow that creates a concentration gradient as the dmg is constantly being removed from its site of absorption 

Plasma protein binding Many drugs are bound to plasma proteins and this helps maintain the concentration gradient because the bound drug is effectively removed 

Active transport mechanisms Of minor importance but drugs related to nutrients can be absorbed more rapidly by transport mechanisms 

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Many laws have been enacted over the last century that affect drug distribution and administration. Those included here are the Pure Food and Drug Act Harrison Narcotic Act Pure Food, Drug, and Cosmetic Act and the Comprehensive Drug Abuse Prevention and Control Act. These laws control the use of the three categories of drugs in the United States (prescription, nonprescription, and controlled substances). 

Palmar M, Broekhoven M, Garrah A, Tu D. CTASSIST a computer program for subjects randomization and tracking of drug distribution. Clin Trials 2000 21 2S 110S. 

GMP versus distribution-chanuel inspection In many countries, GMP inspection receives more attention and resources than inspection of distribution channels. It is true that GMP ensures the quality of a product from the start. But it is not in the interests of the consumer if a product that has been produced according to GMP is later stored and distributed under adverse conditions. Inspection of distribution channels should therefore be given equal emphasis, particularly in countries where the drug distribution system has several intermediate levels and the climate is unfavourable. 

It has been generally assumed that therapeutic serum drug concentration ranges based on data obtained in adults were applicable to children. However, in many instances, when drug response is studied in children, differences in drug distribution and metabolism and in receptor sensitivity rendered this assumption invalid [39]. 

B. Assael, Pharmacokinetics and drug distribution during postnatal development, Pharmacol. Ther. 18, 159-197 (1982). 

Barton, P. Davis, A. M. McCarthy, D. J. Webbom, P. J. H., Drug-phospholipid interactions. 2. Predicting the sites of drug distribution using n-octanol/water and membrane/water distribution coefficients. J. Pharm. Set 86, 1034—1039 (1997). 

Kaufman, J. J. Semo, N. M. Koski, W. S., Microelectrometric titration measurement of the pKa s and partition and drug distribution coefficients of narcotics and narcotic antagonists andtheirpH and temperature dependence, 7. Med. Chem. 18,647-655 (1975). 

KB Bischoff, RG Brown. Drug distribution in mammals. Chem Eng Prog Symp 62 33-45, 1966. 

D Shen, M Gibaldi. Critical evaluation of use of effective protein fractions in developing pharmacokinetic models for drug distribution. J Pharm Sci 63 1698-1702, 1974. 

A simple rocking device was tested for routine determination of distribution coefficients [9], Sample cells were constructed for two-phase [9] and three-phase [10] systems. The investigators claim that the rocking action causes the shape of each phase to vary slowly and constantly and that the precision associated with the distribution coefficient is similar to that for shake-out methods. The three-phase cell was tested as an in vitro model to simulate factors involved in the absorption process. Rates of drug transfer and equilibrium drug distribution were evaluated under conditions in which one aqueous phase was maintained at pH 7.4 and the other phase was maintained at another pH. 

There is evidence for the presence of other human OATPs including OATP-D [30], OATP-F (NM 017435] [39] and OATPRP4 (NM 030958). Further studies are required to determine the impact of these transporters on the drug distribution and elimination. 

Ganapathy V, Prasad PD, Ganapathy ME, Leibach FH. Placental transporters relevant to drug distribution across the maternal-fetal interface. J Pharmacol Exp Ther 2000 294(2) 413-420. 

The CNS contains much smaller amounts of drug-metabolizing enzymes than does the liver. The concentrations of the main enzymes in the brain, members of the cytochrome P450 (CYP) superfamily, are only 0.25% of concentration in the liver. But the brain enzymes are not uniformly distributed, as they are in the liver they are concentrated in specific brain areas. Theoretical models have explained that drug metabolism in the CNS cannot influence drug distribution in the blood, but there are marked differences in brain tissue levels depending on the presence... 

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