EFFECTS OF POOR BIOAVAILABILITY

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The therapeutic effectiveness of a drug depends upon the ability of the dosage form to deliver the medicament to its site of action at a rate and amount sufficient to elicit the desired pharmacological response.

This attribute of the dosage form is referred to as physiologic availability, biologic availability or simply bioavailability. For most drugs, the pharmacologic response can be related directly to the plasma levels.

Thus the term bioavailability is defined as the rate and extent (amount) of absorption of unchanged drug from its dosage form. It can also be defined as the rate and the extent to which the ingredients or active moiety is absorbed from the drug product and becomes available at the site of action1.

As per the definition of bioavailability, a drug with poor bioavailability is one with poor aqueous solubility, slow dissolution rate in biological fluids, poor stability of dissolved drug at physiological pH, poor permeation through biomembrane, extensive presystemic metabolism. Bioavailability of poorly water soluble drugs is a major problem.

A classic example of such drug is saquinavir, a highly potent HIV protease inhibitor, whose minimum effective concentration is only 100 ng/ml, but in order to achieve this concentration, the oral dose required is 1200 mg/day (taken as six 200-mg capsules)2.The reason behind this is the very poor oral bioavailability of saquinavir due to extensive hepatic first pass metabolism. Such a high dose leads to gastrointestinal side effects such as diarrhoea, nausea, abdominal discomfort, dyspepsia, flatulence, vomiting, and abdominal pain.


Some examples of drugs showing poor bioavailability of drugs are shown below:

Drug Aqueous solubility (mg/ml) Absolute bioavailability

Felodipine 0.01900 mg/ml 15%

Ibuprofen 0.04900 mg/ml 49-73%

Candesartan cilexetil 0.00770 mg/ml 15%

Simvastatin 0.00076 mg/ml 5%

Paclitaxel 0.00030 mg/ml 6.5%

This blog is free from plagiarism

REFERENCES:

1. L.Shargel A.B.Yu,(1999).Applied biopharmaceutics&Pharmacokinetics (4th edition) NewYork:McGraw-Hill ,ISBN 0-8385-0278-4

2. http://www.medicinenet.com/saquinavir_oral/Page 3.htm

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Comments

Siva Mavuduru's picture

is lipid solubility or water solubility that determines the bioavailability of a drug?
Dr samrat paul's picture

yes...biological membranes are lipoprotein membranes , even BBB(blood brain barrier)is lipophilic... so lipid soluble drugs are always more bioavailabe than aquous soluble drugs.Only in case of certain disease states, where there is altered permeability of the physiological barriers, eg meningitis and encephalitis, bioavailability for certain drugs change. egs:In meningitis and encephalitis,BBB becomes more permeable and polar antibiotics such as Pn G and ampicillin which do not normally cross it, gain access to the brain. At last what i mean to say that lipid sol or water sol affects both bioavail and distribution as well as other pharmacokinetic parameters. I hope i am right.

samrat

K Rajakrishna's picture

Hello vijay it was a very simple and nice blog to read, can you give a note on the methods that can be used to improve the dissolution of drug with context to bcs classification!.

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