directory of Chem Help ASAP videos: www.chemhelpasap.com/youtube/
Here are two familiar graphs. On the left we have a Cp-time curve for an IV bolus. All the drug is essentially instantaneously injected into the bloodstream of a patient - so not into a muscle or under the skin, intravenous (IV). The drug is initially at a high concentration and then slowly tapers off. If we plot the data as natural log of Cp versus time, then, assuming the drug is behaving as expected, then you will get a straight line. Perfect. Note one thing. The Cp-time curve does not go all the way back to a time of 0. This is not a mistake. Typically, you wait about 15 minutes after administering a drug by IV bolus before drawing blood from a patient and checking Cp levels. Why wait? You are waiting for the drug to undergo distribution.
At the time of an IV injection, the drug is at very high concentration in the blood, especially the plasma fraction of the blood. The drug concentration in the other tissues is low, and the drug will begin distribution from the high-concentration plasma to the low-concentration tissues. The net flow of drug is from the plasma and into the other tissues (muscle, skin, fat, you name it). This early distribution process is fairly fast. How fast? It’s normally complete within about 15 minutes. So, at injection, plasma concentration is sky high. Cp drops rapidly because of distribution and then Cp drops slowly because of natural drug elimination processes, such as hepatic metabolism and renal filtration. Let’s see this distribution process graphically.
Here we go. At time equals 0, Cp is high. Cp drops very quickly until the preliminary distribution phase is complete, and then the curve begins to flatten dramatically. This rapid drop, for most drugs, is complete within 15 minutes. Data points after this rapid drop are what researchers normally track and provide the linear log Cp-time plots that people often show. While these early data points are excluded from curve fitting and PK analysis of the drug, this early spike of drug can pose a safety risk and can represent a high, acute exposure hazard. Therefore, although we ignore these data for PK analysis, we need to be aware of these high Cp values for safety reasons.