Plasma concentration-time profil

To predict oral plasma concentration-time profiles, the rate of drug absorption (Eq. (53)) needs to be related to intravenous kinetics. For example, in the case of the one-compartment model with first-order elimination, the rate of plasma concentration change is estimated as... [Pg.415]

Coupling with its intravenous pharmacokinetic parameters, the extended CAT model was used to predict the observed plasma concentration-time profiles of cefatrizine at doses of 250, 500, and 1000 mg. The human experimental data from Pfeffer et al. [82] were used for comparison. The predicted peak plasma concentrations and peak times were 4.3, 7.9, and 9.3 qg/mL at 1.6, 1.8, and 2.0 hr, in agreement with the experimental mean peak plasma concentrations of... [Pg.415]

Extensions of BCS beyond the oral IR area has also been suggested, for example to apply BCS in the extended-release area. However, this will provide a major challenge since the release from different formulations will interact in different ways with in vitro test conditions and the physiological milieu in the gastrointestinal tract. For example, the plasma concentration-time profile differed for two felodipine ER tablets for which very similar in vitro profiles had been obtained, despite the fact that both tablets were of the hydrophilic matrix type based on cellulose derivates [70], This misleading result in vitro was due to interactions between the gel strength of the matrix and components in the dissolution test medium of no in vivo relevance. The situation for ER formulations would be further complicated by the need to predict potential food effects on the drug release in vivo. [Pg.516]

Fig. 22.3. Mean plasma concentration-time profiles of aciclovir following administration of 1000 mg oral valaciclovir or a 350-mg intravenous infusion of aciclovir over a 1-h period.

Area under the plasma concentration-time profile Chromium-51-labeled ethylenediamine-tetraacetic acid Cytochrome P450, 3A4 isozyme... [Pg.547]

Some idea of the rate of absorption can be obtained from examination of the plasma concentration-time profile. It should be remembered, however, that the time to maximum plasma concentration Y ) is not when absorption is complete but when the rates of drug absorption and elimination are equal. Thus two drugs with the same absorption rate will differ in /max if elimination rates differ. Assessment of the rate of absorption can also be confounded by complex or slow drug distribution. For example, the calcium-channel blocker amlodipine has a much later /max than other similar drugs. This is not due to slow absorption but to partitioning in the liver membrane with slow redistribution. A quantitative assessment of the rate of absorption can be obtained by deconvolution of plasma profiles following IV and oral administration. [Pg.770]

Figure 2 Simulated in vitro drug-release profiles (panels a and b) and resultant plasma concentration—time profiles for a drug with a 1—hr half-life (panel c) and a 6—hr half-life (panel d).

Prototype selection is never wisely made based solely on in vitro dissolution data. This is because the resultant plasma concentration-time profiles are dependent not only on this input rate, but also on the pharmacokinetics of the particular drug. This is illustrated in Figure 2. [Pg.286]

When data are available to enable comparison of the plasma concentration time profile after single administration with that after repeated administration, this would enable determination of whether the substance has time dependent kinetics (due to induction of metabolism, inhibition of metabolism, and/or accumulation and saturation of processes involved in distribution, metabohsm, and excretion). [Pg.100]

Ritalin LA Ritalin LA produces a bimodal plasma concentration-time profile (2 distinct peaks approximately 4 hours apart) when orally administered. [Pg.1154]

Pharmacology Trimetrexate, a 2.4-diaminoquinazoline, nonclassical folate antagonist, is a synthetic inhibitor of the enzyme dihydrofolate reductase. The end result is disruption of DNA, RNA, and protein synthesis, with consequent cell death. Pharmacokinetics Clearance was 38 15 ml /min/m and volume of distribution at steady state (Vdgs) was 20 8 L/m. The plasma concentration time profile declined... [Pg.1925]

Phagocytosis rate increase. Polysaccharide fraction of the fruit, administered to adults at a concentration of 10 pg/mL, was active on polymorphonuclear leukocytes k Pharmacokinetics. Hexane extract of the fruit, administered rectally to 12 healthy male adults at a dose of 640 mg, produced bioavailability similar to that observed for the oral formulations. Extract, administered orally to healthy males at a dose of 320 mg (1 X 320 mg capsule, new formulation or 2 X 160 mg, reference preparation) for 1 month, produced a rapid absorption with a peak time (T J of 1.5-1.58 hour and peak plasma level (C J of 2.54-2.67 pg/mL. The area under the curve value ranged from 7.99 to 8.42 pg/hour/mL. The plasma concentration-time profile of both preparation was nearly identical. Both preparations can be considered as bioequivalenp Hexane ex-... [Pg.471]

FIGURE 4.3 Plasma concentration time profile of drug with a half-life of 4 hours administered every 8 hours. Steady state is reached after 4-5 times the half-life. The concentration time curve after the first dose shows the area under the curve (AUCJ after a single oral dose that is equivalent to the AUC at steady state (AUCss). The broken lines represent the therapeutic range (arbitrary). [Pg.47]

FIGURE 4.4 A Lithium plasma concentration time profile based on a population pharmacokinetics model (Taright et al., 1994). Closed circles are the actual measured lithium concentrations broken lines represent the therapeutic range (0.6-1.2 mmol/L). B Individualized lithium plasma concentration time profile based on the population model with feedback of measured concentrations (Bayesian recalculation). Closed circles are the measured lithium concentrations. The second part of the curve is the predicted lithium concentration profile after increasing the dose to 1000 mg lithium carbonate twice daily, based on a target of 0.6-1.2 mmol/L (broken lines). [Pg.52]

Calculate the plasma concentration time profile using convolution techniques or other appropriate modeling techniques and determine whether tlie lots with the fastest and slowest release rates that are allowed by the dissolution specifications result in a maximal difference of 20% in the predicted Cmax and AUC. [Pg.462]

Figure 3.25 Log10 plasma concentration time profile for a foreign compound after intravenous administration. The plasma half-life (fo) and the elimination rate constant (fce ) of the compound can be determined from the graph as shown.

Fexofenadine mean plasma concentration-time profile obtained using corresponding calibration curves on opposite column... [Pg.26]

Figure 1.6. Fexofenadine calibration curves and mean plasma concentration-time profiles following a single oral administration of (a) 100 pug (microdosing) or (b) 60 mg (clinical dosing) fexofenadine to healthy volunteers. (Reprinted with pemnission from Yamane et al., 2007.)...

Figure 2.2. Plasma concentration time profile following IV dosing.

Various PK parameters such as CL, Vd, F%, MRT, and T /2 can be determined using noncompartmental methods. These methods are based on the empirical determination of AUC and AUMC described above. Unlike compartmental models (see below), these calculation methods can be applied to any other models provided that the drug follows linear PK. However, a limitation of the noncompartmental method is that it cannot be used for the simulation of different plasma concentration-time profiles when there are alterations in dosing regimen or multiple dosing regimens are used. [Pg.96]

FIGURE 2.6 Mean plasma concentration-time profiles following intrajejunal administration of 10 mg/kg of nucleotides ISIS 2503 and ISIS 104838 with 25, 50, and 100 mg/kg sodium caprate (Ci0) in pigs (n = 8). (From Raoof, A.A. et al., Eur. J. Pharm. Sci., 17, 131, 2002. With permission from Elsevier.)... [Pg.47]

Figure 13.2 Plasma concentration-time profile with a programmable drug...

Figure 6.5 Plasma concentration time profile for oral exposure to a toxicant and depiction of AUCs determined by summation of trapezoids at several time periods.

In conclusion, pharmacokinetics is a study of the time course of absorption, distribution, and elimination of a chemical. We use pharmacokinetics as a tool to analyze plasma concentration time profiles after chemical exposure, and it is the derived rates and other parameters that reflect the underlying physiological processes that determine the fate of the chemical. There are numerous software packages available today to accomplish these analyses. The user should, however, be aware of the experimental conditions, the time frame over which the data were collected, and many of the assumptions embedded in the analyses. For example, many of the transport processes described in this chapter may not obey first-order kinetics, and thus may be nonlinear especially at toxicological doses. The reader is advised to consult other texts for more detailed descriptions of these nonlinear interactions and data analyses. [Pg.109]

Figure 2 Mean ( SE, n = 3) plasma concentration-time profile of halofantrine ( ) and desbutylhalofantrine ( ) after fasted oral administration of 150 mg Hf without keto-conazole (closed symbols) or after pretreatment with ketoconazole (open symbols). When Hf was co-administered with ketoconazole, the concentration of Hfm at all time points was below the LOQ of the assay, which was 10 ng/mL. [Pg.106]

After IV application, peptides and proteins usually follow a biexponential plasma concentration-time profile that can best be described by a two-compart-ment pharmacokinetic model [13]. The central compartment in this model represents primarily the vascular space and the interstitial space of well-perfused organs with permeable capillary walls, especially fiver and kidneys, while the peripheral compartment comprises the interstitial space of poorly perfused tissues such as skin and (inactive) muscle [4]. [Pg.28]

A plasma concentration-time profile that is poly-phasic with rapid distribution half-life (< 1 h) and long elimination half-life reflecting slow elimination from the tissues. [Pg.96]

The pharmacokinetic profile of 2 -MOE partially modified ASOs was similar in mice, rats, dogs, monkeys, and humans in that the drug was cleared within hours from the plasma and distributed to the tissues. Following IV administration, the plasma concentration-time profiles of 2 -MOE partially modified ASO are poly-phasic, characterized by a rapid distribution phase (half-lives of 30-80 min), followed by at least one additional much slower elimination phase with half-lives reported from 10 to 30 days. The recent development of ultrasensitive hybridization ELISA methods have made it possible to follow plasma concentrations for up to three months after dose administration, enabling the investigators to determine terminal plasma elimination half-lives [24, 26, 30, 31]. Representative plasma concentration-time profiles with the rapid distribution phase along the slow terminal elimination phase in monkeys and humans for a 2 -MOE partially modified ASO, ISIS 104838 are shown in Figure 4.2 [26]. [Pg.97]

In the application described by Olah and workers, LC/MS-based methods are used to simultaneously assay plasma concentrations of up to 12 substances. The plasma is obtained from either single animals dosed with mixtures of lead compounds, or from multiple animals dosed with a single lead compound, after which aliquots of plasma from common time points are pooled. Essentially, simplified, less stringent versions of preclinical/clinical development procedures are used for sample preparation, assay validation, and analysis. A plasma concentration-time profile obtained from a dog administered simultaneously with 12 compounds is shown in Figure 6.21. Each... [Pg.109]

Several quantitative pharmacokinetic terms are used to describe and quantify aspects of the plasma concentration-time profile of an administered drug (or its metabolites, which may or may not be pharmacologically active themselves). These include ... [Pg.49]

It was noted in the previous section that both pharmacokinetics and pharmacodynamics are concerned with relationships over time. One illustration of the fundamental importance of the rates of these processes can be seen in the plasma concentration-time profile (also known as the plasma-concentration curve) for an administered drug. This was introduced in Section 4.2.1, along with several quantitative pharmacokinetic terms used to describe and quantify aspects of the plasma concentration-time profile ... [Pg.146]

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