Pharmacokinetic parameters terminal half-life

Improved pharmacokinetic behavior was also seen with the microemulsion in many other studies. Inter- and intraindividual variabilities of cyclosporine primary pharmacokinetic parameters (Cmax, /max, AUC, and terminal half-life) were compared following the administration of the two formulations to 24 healthy volunteers. Both inter- and intraindividual variabilities were significantly reduced with the microemulsion intraindividual variability ranged between 9% and 22% for the microemulsion, compared with 19%-41% for the standard formulation, and the interindividual variability values were 3%-22% and 20%-34%, respectively [40],... 

Plasma caffeine and paraxanthine Descriptive pharmacokinetic parameters (standard parameters including peak concentrations (Cmax), time of Cmax (Tmax), area-under-the-curve (AUC) between time 0 and time t where t = 24 h post dose (AUCo-t), AUC after extrapolation to infinity (AUCo-co), apparent terminal half-life total clearance (CL)) for... 

To overcome the pharmacokinetic problems of CSA, a microemulsion formulation was developed. Both forms are available commercially in the United States, referred to as cyclosporine, USP and cyclosporine, USP [MODIFIED]. The two formulations are not bioequivalent and should not be used interchangeably. The microemulsion formulation is self-emulsifying and forms a microemulsion spontaneously with aqueous fluids in the gastrointestinal tract, making it less dependent on bile for absorption. The result is a sig-niflcantly greater rate and extent of absorption and decreased intraindividual variability in pharmacokinetic parameters. Bioavailability is enhanced owing to better dispersion and absorption and does not require bile excretion. The relative bioavailability of the microemulsion formulation is 60%. Peak concentrations generally are reached within 1.5 to 2 hours after oral administration. The terminal half-life is 8.4 hours. 

In pharmaceutical research and drug development, noncompartmental analysis is normally the first and standard approach used to analyze pharmacokinetic data. The aim is to characterize the disposition of the drug in each individual, based on available concentration-time data. The assessment of pharmacokinetic parameters relies on a minimum set of assumptions, namely that drug elimination occurs exclusively from the sampling compartment, and that the drug follows linear pharmacokinetics that is, drug disposition is characterized by first-order processes (see Chapter 7). Calculations of pharmacokinetic parameters with this approach are usually based on statistical moments, namely the area under the concentration-time profile (area under the zero moment curve, AUC) and the area under the first moment curve (AUMC), as well as the terminal elimination rate constant (Xz) for extrapolation of AUC and AUMC beyond the measured data. Other pharmacokinetic parameters such as half-life (t1/2), clearance (CL), and volume of distribution (V) can then be derived. 

The advantages of using non-compartmental methods for calculating pharmacokinetic parameters, such as systemic clearance (CZg), volume of distribution (Vd(area))/ systemic availability (F) and mean residence time (MRT), are that they can be applied to any route of administration and do not entail the selection of a compartmental pharmacokinetic model. The important assumption made, however, is that the absorption and disposition processes for the drug being studied obey first-order (linear) pharmacokinetic behaviour. The first-order elimination rate constant (and half-life) of the drug can be calculated by regression analysis of the terminal four to six measured plasma... 

Pharmacokinetis were evaluated in 15 pts. Mean plasma concentrations oftotal-DXR, free-DXR, encapsulated-DXR at level 4 was shown in Fig 2. Table 4 shows the mean pharmacokinetic parameters of total-DXR, free-DXR-and metabolites in plasma at level 1 to level 4. The plasma concentration of total-DXR at each level reached Cmax at the end of infusion. The plasma concentration profiles of total-DXR at level 1 to 3 showed biphasic elimination pattern but showed monophasic elimination pattern at level 4, because one subject at level 4 showed monophasic elimination pattern with a long half-life. CL, Vdss, and MRT of total-DXR were almost the same among dose levels. T1/2A.Z of total-DXR was prolonged by dose escalation, because the concentration of terminal phase was detected as dose increased (Table 4). Most oftotal-DXR could exist in circulating blood as an encapsulated form, because plasma concentration of... 

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