Absorption time, mean

When a single-dose intravenous and an oral (or other extravascular) plasma curve are both available from the same subject(s) one can define the mean absorption time MAT by means of the mean residence time obtained from the intravenous curve MRT, and the extravascular curve MRT ... 

Mean residence time, mean dissolution time, mean absorption time... 

Figure 10 Mean observed concentration-time profiles for the three extended-release formulations, fast ( ), medium (o), and slow ( ), whose in vitro dissolution data are shown in Figure 3 (panel a) and the derived mean absorption-time profiles (panel b).

Mean Absorption Time The mean time required for drug to reach systemic circulation from the time of drug administration. This term commonly refers to the... 

MAT Mean absorption time Single-dose crossover Less sensitive to discrete sampling issues May mask absorption profile differences... 

Pharmacokinetic Measures of Systemic Exposure Both direct (e.g., rate constant, rate profile) and indirect (e.g., Cmax, Tmax, mean absorption time, mean residence time, Cmax normalized to AUC) pharmacokinetic measures are limited in their ability to assess rate of absorption. This guidance, therefore, recommends a change in focus from these direct or indirect measures of absorption rate to measures of systemic exposure. Cmax and AUC can continue to be used as measures for product quality BA and BE, but more in terms of their capacity to assess exposure than their capacity to reflect rate and extent of absorption. Reliance on systemic exposure measures should reflect comparable rate and extent of absorption, which in turn should achieve the underlying statutory and regulatory objective of ensuring comparable therapeutic effects. Exposure measures are defined relative to early, peak, and total portions of the plasma, serum, or blood concentration-time profile, as follows ... 

B Statistical moments mean dissolution time (MDT) Statistical moments mean residence time (MRT), mean absorption time (MAT), etc... 

Pharmacokinetic Tools to Characterize Absorption Kinetics. The sustained character of lung absorption is important for the degree of pulmonary selectivity. It is therefore important to evaluate lung absorption with pharmacokinetic tools. Several tools have been used to provide this information, including the time to reach the maximum plasma concentration (tmax), the mean absorption time (MAT), flip-flop, and deconvolution. These approaches are described next. 

In this equation. Dose is the administered dose, F is fraction absorbed, MAT is the mean input time or mean absorption time, N A is the normalized variance of the Gaussian density function, and T is the modulus time following administration of a dose. 

A characteristic of artemisinin and its related endoperoxide drugs is the rapid clearance of parasites in the blood in almost 48 horns. Titulaer obtained pharmacokinetic data for the oral, intramuscular and rectal administration of artemisinin to volunteers [132], Rapid but incomplete absorption of artemisinin given orally occurs in humans with a mean absorption time of... 

D, dose F, bioavailability fr, fraction of dose undergoing first-order input in a dual absorption model K, zero-order input rate L and k, first-order absorption rate constants MAT, mean absorption time NV, normalized variance of Gaussian density function, t, nominal time ti g, duration of time-lag x, duration of rapid input in dual absorption model Ti f, duration of zero-order IV infusion T, modulus time. 

MAT(ABSORPnON), is the average time it takes the bioavailable drug molecules after entering the absorption space to enter the disposition space. This MAT is commonly referred to as the mean absorption time. The MAT(ABSORPTION) can generally be calcnlated from the absorption rate,/(0, according to s... 

As discussed, a number of studies have examined the effect of vasoactive drugs on percutaneons absorption. We therefore limit this discnssion to the more detailed investigations. Mnch of this early work was undertaken nsing both the IPPSF (Riviere and Williams, 1991) and anesthetized weanling pig model (Riviere etal., 1992). They reported that the vasodilator tolazoline significantly increased lidocaine flux compared to that observed in vitro, whereas norepinephrine (a vasoconstrictor) sigruficantly decreased lidocaine flux in the IPPSF (Riviere and Williams, 1991). Tolazoline shortened and norepinephrine increased the mean absorption time. Neither of these effects conld be replicated in the in vitro model. Their subsequent work in the anesthetized pig model showed that, in tissue samples taken 4 h after a 1-h iontophoretic treatment period, tolazoline had decreased underlying tissue concentrations of lidocaine, and norepinephrine had increased tissue levels compared to those observed when lidocaine was administered alone (Riviere etal., 1992). Subsequently, Williams and Riviere (1993) used a three-compartment pharmacokinetic model to describe these results. 

In recent years, non-compartmental or model-independent approaches to pharmacokinetic data analysis have been increasingly utilized since this approach permits the analysis of data without the use of a specific compartment model. Consequently, sophisticated, and often complex, computational methods are not required. The statistical or non-compartmental concept was first reported by Yamaoka in a general manner and by Cutler with specific application to mean absorption time. Riegelman and Collier reviewed and clarified these concepts and applied statistical moment theory to the evaluation of in vivo absorption time. This concept has many additional significant applications in pharmacokinetic calculations. 

Substitution of the right side of Eq. A.53 for dX in Eq. A.6, followed by cancellation of FXo in numerator and denominator, yields the following expression for MRT in the gastrointestinal tract (more commonly expressed as mean absorption time [MAT]) ... 

For a dmg administered orally, MRT is the sum of time spent in the gastrointestinal tract (mean absorption time) as well as time spent in the rest of the body. In the case of a one-compartment model drug, the mean absorption time is actually equal to the reciprocal of the absorption rate constant (Eq. A.55) and is, therefore, proportional to the absorption half life. For non-compartmental analysis, the mean absorption time is still a good indicator of the rate of drug absorption. In order to get an estimate of mean absorption time in the non-compartmental situation, the drug is administered both orally and intravenously to a subject. Then ... 

MRT is the sum of the MRT values for each individual process, MRTiv represents the distribution and elimination processes occurring for both the oral and intravenous doses. Therefore, subtracting MRTiv from MRTorai will yield the MRT for the absorption process, namely the mean absorption time (MAT). 

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... 

A study in 18 healthy subjects found that rifampicin 600 mg daily for 10 days decreased the maximum plasma level of a single 1-g dose of dicloxacillin by 27% and increased the mean oral clearance by 26%. The mean absorption time increased from 0.71 to 1.34 hours. Rifampicin increased the formation clearance, maximum level and AUC of the 5-hy-droxymetabolite of dicloxacillin by 135%, 119%, and 59%, respectively. Dicloxacillin is a substrate of P-glycoprotein and it was suggest that the... 

The rate of absorption can be characterized from the calculation of Zresidence fot both i.v. administration and non-i.v. administration. The mean absorption time (tabsorption) is calculated as the difference of the two mean residence times. 

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