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Prof Dr dr Jazanul Anwar SpFK

Dept Farmakologi dan Terapetik FK USU

Overview - ADMEA
Most drugs : enter the body (by mouth or injection or) - must cross barriers to entry (skin, gut wall, alviolar membrane..) are distributed by the blood to the site of action - intra- or extracellular - cross barriers to distribution (capillaries, cell wall.) - distribution affects concentration at site of action and sites of excretion and biotransformation

are biotransformed perhaps to several different compounds by enzymes evolved to cope with natural materials - this may increase, decrease or change drug actions
are excreted (by kidney or .) which removes them and/or their metabolites from the body Pharmacokinetics is the quantification of these processes

Drug Absorption
absorption dissolution disintegration gastric emptying rate
intestinal metabolism hepatic metabolism

intestinal transit rate

absorption disintegration

Drug excretion

Drug Excretion -most drugs are excreted in urine either as unchanged or drug metabolites

Renal Function
1. Glomerular filtration 2. Active tubular secretion 3. Passive tubular reabsorption 4. Excretion

Elimination by the Kidney

Excretion - major 1) glomerular filtration glomerular structure, size constraints, protein binding

2) tubular reabsorption/secretion - acidification/alkalinization, - active transport, competitive/saturable, organic acids/bases - protein binding
Metabolism - minor

Excreted drug = (Filtered+ secreted) - reabsobed

Glomerular Filtration- 1st step in renal drug excretion

Drug enters renal tubule as a dissolved solute Drug filtration rate= Free drug Plasma conc. X Glomerular filtration rate (GFR)

For Penicilin G- 40% unbound in plasma;

pKa= 2.8; Plasma conc.=3 mg/mL; Free drug conc.= ? Drug excretion rate- 1200 mg/min Glomerular filtration rate- 100 mL/min

Excretion of drugs
Routes of excretion

1- Renal Excretion: It is the result of three processes:

Passive glomerular filtration, active tubular secretion in proximal tubules and passive tubular re-absorption. Factors affecting renal excretion: 1-Glomerular filtration rate. Only free unbound water soluble drugs with low molecular weight are filtered.

2-Change in urinary pH affect excretion of weak acid and base drugs. Thus: -Alkalinization of urine by NaHCO3 increases of acidic drugs e.g. aspirin.
-Acidification of urine by NH4CL or vitamin C increases excretion of base drugs e.g., amphetamine. 3-Active tubular secretion e.g., probenecid, penicillin, uric acid ...

Passive Reabsorption -most substances are reabsorbed across renal tubular cells if unionized and lipid soluble Can manipulate urine pH to ensure drugs are not reabsorbed in overdose situations 5.8 = 5.8 + log A-/HA= 1= 1:1 Rate of reabsorbtion = 1.2 mg/mL x 1/2 = 0.6 mg/mL increase urine pH to 7.0

7.0 = 5.8 + log A-/HA= 1.2 = 15.8:1= 1.2 mg/mL x 1/16.8 = 0.071 mg/mL

Renal Clearance= excretion rate/plasma drug concentration (units: L/h) For penicilin: 1200 ug/min/ 3ug/mL= 400 mL/minx60 min/h=24000mL/h= 24000mL/hX 1L/1000mL= 24L/h

Excretion of drugs
2-Gastrointestinal Tract: a. Salivary glands: e.g., iodides, rifampicin and acidic drugs as salicylates. b. Stomach: e.g., morphine (free and conjugated). c. Large intestine: e.g., tetracycline, streptomycin. d. Liver through bile, e.g. -Ampicillin and rifampicin are excreted in active form so can be used in biliary infection and ampicillin in typhoid carriers.


Other routes of excretion:

Biliary excretion- drugs with mwts >300 excreted in to bile

Enterohepatic cycling-

Sweat, Saliva-


3-Sweat: e.g., rifampicin, vitamin B1.


4-Lungs: e.g., gases and volatile anesthetics.


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5-Milk: basic drugs are trapped and excreted in acidic milk, e.g., morphine, ampheta. Also chloramphenicol and oral anticoagulants can be excreted in milk.


IV. OTHER ROUTES A. Hair drugs heavy metals

B. Tears
Rifampin + =

Soft contact lens