Area under plasma concentration-time

Table 2 Peak Plasma Levels and Areas Under Plasma Concentration Time Curves Following Oral and Intravenous Administration to Men...

AU G Area under plasma concentration time curve... 

The influence of some of the aforementioned factors on aluminum absorption is further illustrated by the findings of two animal studies which estimated bioavailability differences by comparing areas under plasma concentration-time curves (AUC) after oral and intravenous dosing (Yokel and McNamara 1988). Using a single oral dose of aluminum chloride, aluminum absorption was estimated to be 0.57% in... 

ABBREVIATIONS AUC, area under plasma concentration-time curve tj, elim, half-life of elimination t, increase -i, decrease [Pg.842]

Following the administration of a drug by an intravenous injection, if it is necessary to use a two-compartment model, the area under the plasma concentration-time curve from f = 0 to f = f (the last sampling time) may be estimated by using trapezoidal rules, as mentioned earlier. Additionally, the area under plasma concentration-time curve from f = f to f = may be computed using the following equation ... 

Famciclovir can be given with or without food. The most common adverse effects are headache and Gl disturbances. Concomitant use of famciclovir with probenecid results in increased plasma concentratiens of penciclovir. The recommended dose of famciclovir is 500 mg every 8 hours for 7 days. The absolute bioavailability of famciclovir is 77%, and the area under plasma concentration-time curve (AUC) is 86 pg/mL. Famcicicvir with digexin increased plasma ccncentraticn cf digexin tc 19% as compared to digoxin given alone. 

AUC-area under plasma concentration-time curve 0 to 24 h, 7 ,ax-CPmax-plasma concentration at peak From [227]. 

Pharmacokinetic parameters such as area under the concentration-time curve (AUC) and maximal plasma concentration can be predictive of treatment outcome when specific ratios of AUC or maximal plasma concentration to the minimum inhibitory concentration (MIC) are achieved. For... 

Commercial samples containing approximately 400 mg of ephedra per capsule yield roughly 5 mg of ephedrine, 1 mg of pseudoephedrine, and less than 1 mg of methylephedrine (White et al. 1997). For a dose of four capsules, yielding approximately 20 mg of ephedrine, the elimination half-life is 5.2 hours. The time to reach maxium concentration is 3.9 hours. Compared to pure ephedrine tablets, the elimination kinetics of ephedra are comparable. However, ephedra showed somewhat different absorption kinetics (e.g., lag time, area under the concentration-time curve, and maximum plasma concentration). So, ephedra tablets may vary from pure ephedrine in the onset of action, but the durations of action are grossly equivalent. 

Sohn et al. [148] examined the kinetic variables of omeprazole and its two primary metabolites in plasma, 5-hydroxyomeprazole and omeprazole sulfone, and the excretion profile of its principal metabolite in urine, 5-hydroxyomeprazole, in eight extensive metabolizers and eight poor metabolizers. Each subject received a postoral dose of 20 mg of omeprazole as an enteric-coated formulation, and blood and urine samples were collected up to 24 h postdose. Omeprazole and its metabolites were measured by HPLC with UV detection. The mean omeprazole area under the concentration-time curve, elimination half-life, and apparent postoral clearance were significantly greater, longer, and lower, respectively, in the poor metabolizers than in the extensive metabolizers. The mean cumulative urinary excretion of 5-hydroxyomeprazole up to 24 h postdose was significantly less in the poor metabolizers than in the extensive metabolizers. 

Pharmacokinetic Profile of the Compound (Exposure) For toxicokinetic purposes it is usually sufficient to describe the systemic burden in plasma or serum of the test species with the test compound and/or its metabolites. The area under the matrix level concentration-time curve (AUC) and/or the measurement of matrix concentrations at the expected peak-concentration time Cmax, or at some other selected time1 C(time), are the most commonly used parameters. According to the supplementary notes in the ICH Guidance Toxicokinetics 1994 for a profile (e.g. 4 to 8) matrix samples during a dosing interval should be taken to make an estimate of Cmax and/or C(time) and area under matrix concentration time curve (AUC). 

The importance of tissue penetration varies with the site of infection. The CNS is one body site where the importance of antimicrobial penetration is relatively well defined and correlations with clinical outcomes are established. Drugs that do not reach significant concentrations in cerebrospinal fluid should either be avoided or instilled directly when treating meningitis. Apart from the bloodstream, other body fluids where drug concentration data are clinically relevant include urine, synovial fluid, and peritoneal fluid. Pharmacokinetic parameters such as area under the concentration-time curve (AUC) and maximal plasma concentration can be predictive of treatment outcome when specific ratios of AUC or maximal plasma concentration to the minimum inhibitory concentration (MIC) are achieved. For... 

Plasma area under the concentration—time curves (AUCs) of 57 NCEs were determined following oral cassette administration (5—9 NCEs/cassette) to mice. Physicochemical properties [such as, molecular weight, calculated molar refractivity, and calculated lipophilicity (clogP)] and molecular descriptors [such as presence or absence of N-methylation, cyclobutyl moiety, or heteroatoms (non-C,H,0,N)] were calculated or estimated for these compounds. This structural data, along with the corresponding pharmacokinetic parameters (primarily AUC), were used to develop artificial neural network models [8]. These models were used to predict the AUCs of compounds under synthesis [10]. This approach demonstrates that predictive models could be developed which potentially predict in vivo pharmacokinetics of NCEs under synthesis. Similar examples have been reported elsewhere [11—13]. 

The area under the concentration-time curve (AUC) and the peak plasma concentration (Cmax) from the predicted prohles are compared to those obtained from the observed prohles to calculate the percent prediction errors. 

Finally, the method used to calculate the volume of distribution may be influenced by renal insufficiency. The three most commonly used volume of distribution terms are volume of the central compartment (Ec), volume of the terminal phase (E, E jea). and volume of distribution at steady state (Eis). The central compartment volume is calculated as the intravenous bolus dose divided by the initial plasma concentration. E for many drugs approximates extracellular fluid volume and thus may be increased or decreased by shifts in this physiologic volume. Renal insufficiency, especially oliguric acute renal failure, is often accompanied by fluid overload and a resultant increased Ec due to reduced renal elimination of water and sodium. Uaiea Or E is Calculated as the total body clearance divided by the terminal elimination rate constant (k or /3). This volume term represents the proportionality constant between plasma concentrations in the terminal elimination phase and the amount of drug remaining in the body. E is affected by both distribution characteristics, as well as by the elimination rate constant. The third volume term, the steady-state volume of distribution (Ess), is calculated as (AUMC x dose)/AUC , where AUMC is the area under the first moment of the concentrationtime curve and AUC is the area under the concentration-time curve... 

AUC area under the concentration-time curve AUCo-t the area under the predialyzer plasma concentration-time curve during hemodialysis... 

Concomitant use of topiramate and digoxin has been shown to decrease the area under the concentration-time curve (ADC) for plasma digoxin by 12%, although the clinical relevance is unclear. - ... 

The zero moment in the drug plasma concentration-time curve is the total area under the plasma concentration-time curve from f = 0 to f = , (AUC)q". Estimates of the area under this curve are useful in calculating bioavailability as well as drug clearance, which is the ratio of dose over area under the concentration-time curve for an intravenous dose. 

In Equations 1.5 and 1.6, is a bolus intravenous dose P is the terminal elimination rate constant representing elimination out of the body when the drug follows a two-compartment model a, which is larger than p, is the distribution rate constant AUC is the area under the concentration-time curve for drug in plasma following the intravenous dose and k2i is a model parameter representing distribution of drug from the peripheral compartment into the central compartment. In both of the above equations, the term is equated to an elimination term, P in Equation... 

The PD parameters (e.g., nadir count or the surviving fraction, i.e., the nadir count divided by the pretreatment count) are usually correlated to PK parameters, such as the integral of total drug exposure over time (total area under the concentration-time curve, or AUC), steady-state plasma concentrations during continuous infusion (QJ, or the time above the threshold concentration using linear, log-linear, or models. Table 2.2 lists PD studies of hematological toxicity. 

The objectives of a toxicokinetic program in toxicology studies are outlined in Table 3.5. These objectives may be met by characterizing one or more pharmacokinetic parameters from measurements made at appropriate time points in a toxicology study. The measurements are typically concentrations of the parent drug or metabolite in plasma or serum. However, in some cases it may be more appropriate to sample some other matrix or to quantify tissue levels. The pharmacokinetic parameters are usually area under the concentration-time curve (AUC), and maximum concentration (C ), or the duration that the concentration is above a given threshold (Q. The choice of the pharmacokinetic parameters should be made on a case-by-case basis. 

For data presentation, tissue radioactivity levels are expressed as nanogram-equivalents per gram tissue (Table 18.Al), and tissue/plasma ratios. The maximum concentration (Cmax) and the time to reach maximum concentration (Fmax) are obtained by visual inspection of the raw data. Pharmacokinetic parameters, included half-life (fi/2), area under the concentration-time curve... 

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