First Pass Metabolism
INTRODUCTION & MOA:
- First-pass effect –
- Phenomenon of drug metabolism whereby drug concentration is greatly reduced before reaching systemic circulation & its concerned target tissue.
- Mostly occurs with orally administered drug – Due to vulnerability to metabolizing enzymes in intestinal wall & liver.
- Finally transported via portal vein to liver for metabolization.
- Hence, referred as “Presystemic metabolism”.
- Drug bio-availability is greatly reduced.
- Can be avoided by adminstering drug via sublingual, transdermal or parentral routes.
DRUGS EXPERIENCING FIRST PASS METABOLISM:
- Notable drugs:
- Imipramine, morphine, propranolol, buprenorphine, diazepam, midazolam, demerol, cimetidine, and lidocaine.
ALTERNATIVE ROUTES OF ADMINISTRATIONS:
Avoid first-pass effect because they allow drugs to be absorbed directly into systemic circulation.
- Suppository
- Intravenous
- Intramuscular
- Inhalational aerosol –
- Limited first pass metabolism occurs.
- Especially for drugs via veins.
- Transdermal (via Skin)-
- Limited presystemic metabolism occurs.
- Sublingual or buccal routes – e.g. Isosorbide mononitrate.
EXTENT OF FIRST PASS METABOLISM:
- Refers to drug fraction lost during absorption process that is generally related to liver & gut-wall.
| LOW | INTERMEDIATE | HIGH-NOT GIVEN ORALLY | HIGH ORAL DOSE |
| Phenobarbitone | Aspirin | Isoprenaline | Propranolol |
| Phenylbutazone | Quinidine | Lignocaine | Alprenolol |
| Tolbutamide | Desipramine | Hydrocortisone | Verapamil |
| Pindolol | Nortriptyline | Testosterone | Salbutamol |
| Isosorbide mononitrate | Chlorpromazine | Glyceryl trinitrate | |
| Pentazocine | Morphine | ||
| Metaprolol | Pethidine |
DRUGS PROPERTIES:
- Drugs with high first pass effect have considerably higher oral dose than sublingual or parenteral dose.
- There is marked individual variation in oral dose due to differences in extent of first pass metabolism.
- Oral bioavailability is apparently increased in patients with severe liver diseases like Cirrhosis.
- Increased effect seen if another drug competing with it in first pass metabolism given concurrently.
- Eg. Propranolol & chlorpromazine
Exam Question
- A drug administered through oral route undergo high first pass metabolism.
- High first pass metabolism causes for less bioavailability.
- High first pass metabolism is seen in Lignocaine, Propranolol & Salbutamol.
- Isosorbide mononitrate bypasses first pass metabolism.
- Sublingual route escape first pass metabolism.
- Theophylline escape first pass metabolism.
Don’t Forget to Solve all the previous Year Question asked on First Pass Metabolism