According to statistical moment theory, mean residence time (MRT) is an important measure in pharmacokinetics. MRT can be defined as the expected mean of a probability density function distribution. It provides valuable insights into drug disposition in the body.
After the administration of a drug through intravenous bolus injection, the drug molecules are distributed throughout the body and remain there for varying periods. The MRT represents the average time these drug molecules stay in the body. This parameter is useful for understanding how long a drug remains active or present in the system.
To calculate the MRT, we examine the area under two curves: the moment-versus-time curve and the concentration-versus-time curve. The area under the moment-versus-time curve provides information about the distribution and residence of drug molecules in the body, while the area under the concentration-versus-time curve gives insights into the overall exposure to the drug in the body.
Typically, the calculation of the MRT involves integrating these curves from zero to infinity. However, since it is impossible to measure drug concentrations infinitely, a log-linear terminal phase assumption is made. This assumption allows us to extrapolate the area under the moment-versus-time curve to infinity from a given point.
It is important to note that the calculation of MRT has a major limitation. It can only be accurately calculated after a single-dose administration of a drug and not under steady-state conditions. This means that the MRT value represents the average residence time for a single drug dose rather than a continuous or repeated dosing schedule.
Pharmacokinetic modeling often employs the noncompartmental approach to calculate the MRT. This methodology considers the available data from a single-dose administration and uses various equations and algorithms to estimate the MRT accurately.
In summary, mean residence time is a vital parameter in pharmacokinetics that describes the average time drug molecules remain in the body. It can be calculated using the area under the moment-versus-time and concentration-versus-time curves. However, its calculation is limited to single-dose administrations and requires a noncompartmental approach.
From Chapter 7:
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