Modulation, First - pass effect , Bioavailability & Bioequivalence

Modulation of the cytochrome P450 system

INHIBITION - Drugs inhibit the action of these enzymes and even the isoforms have an important role to play Eg : Quinidine is a potent competitive inhibitor of CYP2D6 and Ketoconazole is a non-competitive inhibitor of CYP3A4

INDUCTION - Some drugs increase the activity of these enzymes and the conjugating systems when administered repeatedly Eg: Rifampicin 

Presystemic metabolism 

 Also called as the First pass effect. Drugs when administered orally undergoes circulation via the hepatic-portal vein from Gut wall to the Liver where part of the drugs are metabolized and only the remaining part of the drug enters the circulation.

source: https://resources.time.leeds.ac.uk/

Disadvantages of First pass effect

1) Lower bioavailability 

source:https://metastatictrialtalk.org/


2) Higher drug dosage 

source: https://www.shutterstock.com


3) Individual variation

source: https://www.Dreamstime.com 


Bioavailability and Bioequivalence

Bioavailability is the fraction of an ingested dose of the drug that gains access to systemic circulation

                          F =AUC(ORAL) / AUC(INTRAVENOUS)

where  AUC – Area under the curve , expressed as g.h/ L

 

Bioequivalence is that if one formulation of a drug is replaced by another , no clinical adverse reactions occur

source:https://www.powershow.com/


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