When drugs are administered extravascularly, a comprehensive evaluation through noncompartmental analysis becomes imperative. This analytical approach considers various parameters that play a crucial role in understanding the pharmacokinetics of these drugs.
One of the key parameters is the mean transit time (MTT), which refers to the total duration required for drug molecules to transit through the body. MTT is determined by calculating the ratio of the area under the moment curve to the area under the concentration-time curve. Doing so provides valuable insights into the drug's mean absorption time (MAT) to reach the systemic circulation and its mean residence time (MRT) within the systemic circulation.
It is worth noting that regardless of the administration route, the mean residence time remains constant. However, the MRT significantly influences the drug's mean absorption and transit times. This observation underscores the importance of considering the residence time when analyzing the pharmacokinetic behavior of extravascularly administered drugs.
In the case of orally administered tablets or capsules, an additional parameter called mean dissolution time (MDT) comes into play. MDT explicitly evaluates the time required for the drug to dissolve in vivo. Its estimation is straightforward for immediate-release-type products, as they exhibit predictable dissolution patterns. In extended-release (ER) formulations, the release of the drug is controlled by various mechanisms, such as matrix systems, coatings, or osmotic pumps, which extend the dissolution process. The extended-release directly increases the MDT compared to immediate-release (IR) formulations.
To calculate the mean dissolution time, we must determine the difference between the mean transit time for a solution and the mean transit time for an immediate-release solid drug product. This distinction provides a valuable indication of the drug's dissolution characteristics and aids in understanding its behavior within the body.
By applying noncompartmental analysis and considering these parameters, researchers and healthcare professionals can understand how extravascularly administered drugs interact with the body, including their transit, absorption, residence, and dissolution processes. This knowledge enables them to make informed decisions regarding dosing regimens, therapeutic efficacy, and potential drug interactions.
From Chapter 7:
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