BIOM 3090 Lecture 7: BIOM 3090 class notes lec 7
9 Jun 2018
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- Distribution
o Absorption of a drug is a requisite for establishing adequate blood
drug levels, but the blood must also reach the target site in adequate
concentrations to be effective
▪ Distribution of drug is achieved primarily through the systemic
circulation with minor contributions from the lymphatic’s
o Once in the systemic circulation, a drug can..
▪ Remain in vascular (blood) space
▪ Distribute to enter interstitial fluid
▪ Further distribute to enter intracellular fluid
o Distribution of drug in the body is affected by..
▪ Physiochemical properties of the drug
• Lipid solubility
• Size (molecular weight)
• Degree of ionization
▪ Anatomy and physiology of patient: tissue perfusion
• Organs and tissues vary widely in the proportion of
systemic blood received
o Initially the vessel-rich tissues (liver, kidney,
brain, heart) receive the greatest cardiac output
and thus distribution of drug
o Distribution of drug to less well-perfused tissues
(muscle, fat, skin, most viscera) is slower, but
accounts for most of the extravascular drug
o Resting tissue and adipose get less blood flow:
liver, kidney, brain and heart get a lot of blood
flow
• Capacity of a tissue to take up drug can be vary (eg. BBB
capillaries mush less permeable to water-soluble drugs)
▪ Non target binding of drug
• Plasma protein binding
o Many drugs circulate in the blood bound to
plasma proteins; can show low → high affinity
proteins
▪ Cannot diffuse from vascular space in
tissues
o Binding involves a saturable, non-linear process
o Albumin (~ 4g/dL) is a major carrier for drugs
that act as weak acids (eg. NSAIDs)
o Alpha1-acid glycoproteins bind drugs weak
bases
• Tissue binding
o Many drugs accumulate in tissues at levels
higher than blood or extracellular fluid; can
prolong drug action
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▪ Bind cellular proteins, phospholipids,
nuclear proteins
▪ Drug distribution and elimination → OBSERVE CHARTS
• Rapid absorption phase and then drop and then
equilibrium to which it stays there
• Drops slowly and quick, eliminated in a linear fashion
o The volume of distribution (Vd) describes the extent to which a drug
partitions between blood and tissue compartments (how much a drug
wants to stay in the cell or go in interstitial fluid or go somewhere
else)
o Total body water (TBW) is approximately 60% body weight (average
human is ~ 70 kg body weight); 70 kg person has ~ 42 L TB or 0.6
L/kg
o Assume 1L water occupies 1 kg
o Vd = amount of drug in body (mg)/plasma drug conc (ug/ml)
find more resources at oneclass.com
find more resources at oneclass.com
