today let's talk about the first pass effect and bioavailability for a drug taken orally or by mouth to reach systemic circulation it first passes from the lumen of a digestive tract into the paddock portal system this system consists of capillary networks the surround organs of the digestive tract such as the stomach in small intestines as well as the hepatic portal vein which carries absorb material to the liver after passing through the liver the drug finally reaches systemic or general circulation or it can be distributed throughout the body to exert its desired action since the liver is the main organ of the body that metabolizes drugs in many cases much of the drug that is taken orally ends up being destroyed by the liver before the drug even makes it to systemic circulation we call this breaking down action by the liver first pass metabolism many drugs have what is called a heavy first pass effect where they are so substantially removed by the liver on the first pass that taking them orally results in very little of the drug reaching systemic circulation for drugs that undergo a heavy first pass effect alternative routes may be used for administration such routes include intravenous rectal subcutaneous and intramuscular inhaled transdermal sublingual buccal aural intra-arterial intranasal in for ocular intravaginal and intra-articular a good example of a drug class that has a heavy first pass effect after oral administration are nitrates used to treat chest pain also called angina because nitrates are metabolized by the liver extensively on first pass they must be given by an alternative route like sublingually topically or intravenously bioavailability is the fraction or percentage of a drug that reaches systemic circulation drugs that are administered by the intravenous route are 100% bioavailable because the entire amount administered makes it to systemic circulation as mentioned oral drugs are not 100% bioavailable because some of the drug is not absorbed but is instead lost in the feces and still again some of the drug is destroyed by the liver before it reaches general circulation please attempt to answer the following question given the following information 300 milligrams of a drug is administered orally 70 percent of the drug is absorbed and the hepatic extraction ratio is 60% what is the overall bioavailability for this drug to answer this question this important equation may be used in the equation F is the overall bioavailability and represents the percentage of drug that makes it to systemic circulation FG is the amount of drug that is absorbed into portal circulation from the gut and this is 70% in our example FH is the percentage of drug in portal circulation that is not destroyed by the liver and makes it past the liver the hepatic extraction ratio is the percentage of drug in portal circulation that the liver takes out and we said that this is 60 percent for our example using this percentage we can find the percentage that escapes the liver by subtracting 60 percent from 100 percent to get 40 percent multiplying F G times F H gives the overall bioavailability which is 70 percent times 40 percent and equals 28 percent remember that bioavailability is always expressed as a percentage using the overall bioavailability one can find the milligrams that actually make it to systemic circulation in this case it would be 28 percent of 300 milligrams which is 84 milligrams please answer the following question to assess your understanding of the first pass effect if you answered a you are correct thanks for watching