Metabolism mean residence time

The truncated part of the integral can be obtained by numerical integration (e.g. by means of the trapezium rule) of the function rCp(r) between times 0 and T. The mean residence time MRT is an important pharmacokinetic parameter, especially when a substantial fraction of the drug is excreted or metabolized during its first pass through an organ, such as the liver. 

The time available for metabolism to occur during diffusion of drug across the length of the cells is approximated by the mean residence time (t) ... 

Following IV administration, 66% of circulating radioactivity was attributed to unchanged drug and the remainder attributed to saquinavir metabolites, suggesting that saquinavir undergoes extensive first-pass metabolism. Systemic clearance of saquinavir was rapid, 1.14 L/h/kg after IV doses of 6, 36, and 72 mg. The mean residence time of saquinavir was 7 hours. 

Veng-Pedersen, P, Mean time parameters in pharmacokinetics. Definition, computation and clinical implications (Part II), Clin. Pharmacokinet., 17 424 40, 1989. Veng-Pedersen, R, Mean time parameters in pharmacokinetics. Definition, computation and clinical implications (Part I), Clin. Pharmacokinet., 17 345-366, 1989. Aarons, L., Mean residence time for drugs subject to reversible metabolism, J. Pharm. Pharmacol., 39 565-567, 1987. 

Cheng, H. and Jusko, W. J., Mean residence time of oral drugs undergoing first-pass and linear reversible metabolism, Pharm. Res., 10 8-13, 1993. 

There are good examples from the metabolic literature of studies in which the number of data observed for a single subject is limited. An example is measuring the mean residence time of low density lipoprotein in the rabbit aortic wall (Schwenke and Carew, 1989). In experiments such as these, samples of the aorta may only be obtained once, at the end of the experiment. Thus there is only one datum for each tracer used. Schwenke and Carew (1989) used two iodine tracers, administered at different times, but the compartmental model they used has four parameters. Clearly, parameter values cannot be estimated for each animal without using information from experiments in other animals. 

Km the first-order rate constant for metabolism of dmg or [in context] the Michaelis constant in non-linear pharmacokinetics Ko the zero-order elimination rate constant Mother the first-order rate constant for elimination of dmg by a process other than metabolism or renal excretion Kio for a two-compartment dmg, the first-order rate constant for elimination of dmg from the central compartment Ki2 for a two-compartment drug, the first-order rate constant for transfer from the central to the peripheral compartment K21 for a two-compartment drug, the first-order rate constant for transfer from the peripheral to the central compartment MAT mean absorption time mean residence time in the gastrointestinal tract synonymous with MRTgit... 

The experimental data of plasma and urine radioactivities were analyzed by the non-compartmental approach (Rescigno and Gurpide, 1973), as described in details previously (Bianchi et al., 1979). The formulas utilized in this approach allow to determine the following parameters of uric acid kinetics total metabolic clearance rate (MCR), mean residence time of the tracer, total distribution volume (TDV, plasma equivalent), fractional catabolic rate (FCR, relative to TDV), and clearance rate of C-uric acid via the renal route (MCR] ). The total turnover rate (TR) and the total pool of exchangeable uric acid are then obtained as the product of, respectively MCR or TDV by the plasma urate concentration. The extrarenal disposal of uric acid (bacterial uricolysis in the gut, skin desquamation) is determined as the difference between the total metabolic clearance rate and the clearance rate of uric acid through the kidney route. 

The radioactivity detector has an obvious application in metabolic studies. Unfortunately it is necessary when using this detector to trade resolution and speed for sensitivity. The response of the radioactivity detector is a function of the total amount of radioactivity in the detector cell, which means that the detector cell should be as large as possible. On the other hand a large cell volume will cause dispersion of the chromatographic peaks, and a compromise must therefore be found. The response is also a function of the residence time of the solute in the cell, calling for slow pumping velocity of the mobile phase, thus giving increased time of analysis. 

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