Area under the concentration time curve

Mean clearance (CL) values for cetuximab are displayed as a function of dose in Fig. 14.3. Mean CL values decreased from 0.079 to 0.018 L/h/m2 after single cetuximab doses of 20 to 500 mg/m2, respectively. In the dose range 20 to 200 mg/m2, CL values decreased with dose. At doses of 200 mg/m2 and greater, CL values leveled off at a value of approximately 0.02 L/h/m2. This biphasic behavior suggests the existence of two elimination pathways. The elimination of cetuximab apparently involves a specific, capacity-limited elimination process that is saturable at therapeutic concentrations, in parallel with a nonspecific first-order elimination process that is non-saturable at therapeutic concentrations. Increasing doses of cetuximab will therefore ultimately lead to the saturation of the elimination process that is capacity-limited and that follows Michaelis-Menten kinetics, whereas the first-order process will become the dominant mechanism of elimination beyond a particular dose range. 

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In 1950 French " and Wideqvist independently described a data treatment that makes use of the area under the concentration-time curve, and later authors have discussed the method.We introduce the technique by considering the second-order reaction of A and B, for which the differential rate equation is... 

As the amount in the body decreases, the concentration decreases by the same law (-dC/d/ = Ke C), i.e., first-order kinetics resulting in an exponential function. The integral is the area under the concentration time curve (ACC). 

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. 

In patients taking rifabutin, protease inhibitors can significantly increase the area under the concentration-time curve. High concentrations of rifabutin can provoke uveitis. If the combination of rifabutin and a protease inhibitor is essential, dose adjustments are recommended. 

Abbreviations CYP, cytochrome P-450 CYP3A4, cytochrome P-450 3A4 AUC, area under the concentration time curve EM, extensive metabolizer PM, poor metabolizer. 

Indinavir is a protease inhibitor used in the management of HIV infection. CYP3A4 mediates the biotransformation of indinavir in vitro (85,86), and in vivo, indinavir has been shown to be a potent competitive and mechanism-based inhibitor of CYP3A4 (85,87). Piscitelli and coworkers (80) examined the effect of St. John s wort (300 mg t.i.d. x 14 days) administration on indinavir (800 mg q.i.d. x 8 hr x four doses) exposure in eight healthy volunteers (two females). The administration of St. John s wort for 14 days resulted in a significant 54 /o reduction in the indinavir eight-hour area under the concentration-time curve, from 35.8 13.0 to 15.6 5.8 pg X hr/mL. The authors conclude that the magnitude in the reduction in indinavir concentrations may result in the development of antiretroviral resistance and subsequent treatment failure. 

Compared to baseline saquinavir pharmacokinetic parameters obtained in period 1, the use of garlic reduced the mean saquinavir area under the concentration-time curve (AUC) by 51%, and the maximum (Cmax) and minimum (Cmin) saquinavir concentrations by 54% and 49%, respectively. After a 10-day washout, the AUC, Cmax, and Cmin values were within a range of 60% to 70% of baseline values. The magnitude of the decline in concentration might result in therapeutic failure and viral rebound in patients with HIV. Based on the pharmacokinetic parameters obtained in period 3, it also appears that garlic might have a prolonged, albeit lesser, effect on saquinavir exposure. The effects of combined treatment with other protease inhibitors that are also potent cytochrome P-450 (CYP) enzymes modulators need to be further evaluated. 

Clearance can be calculated from the area under the concentration-time curve (AUC area under the curve) following bolus administration C/=Dose/AUC. This can be used for any form of intravenous administration and does not rely on compartmental analysis. 

Verapamil and its active metabolite norverapamil were assayed from serum (frozen at -18°C) using a gas chromatographic-mass spectrometric method [5]. The detection limit of the method was 1 ng/ml. The areas under the concentration-time curves (AUC 0-32 h) were calculated by the trapezoidal method. Statistical evaluation was carried out using the paired Wilcoxon test and paired Student s t test. 

Target area under the concentration time curve after a single dose. 4... 

An instantaneous pulse of tracer is injected into the stream entering the vessel. The outlet response, normalised by dividing the measured concentration C by A , the area under the concentration-time curve, is called the C-curve . 

Note ACE = angiotensin-converting enzyme INR = international normalized ratio PT = prothrombin time PTT = partial thromboplastin time ECG = electrocardiogram PAF = platelet-activating factor AUC = area under the concentration/time curve. 

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. 

Abbreviations Crmx maximum cetuximab serum concentration AUCo-ob area under the concentration-time curve extrapolated to infinity CL total body clearance Vss volume of distribution at steady state terminal elimination half-life SD standard deviation. 

Abbreviations Cm T, maximum measured drug concentration Tmax, time to reach Cmax AUC, area under the concentration-time curve CLr, renal clearance F, bioavailability. 

Mean values SD for all parameters. ap < 0.05 compared to control. bp < 0.001 compared to control. cp < 0.005 compared to control. Abbreviations. Cmax, maximum measured drug concentration Tmax, time to reach Cmax AUC, area under the concentration-time curve r1/2, terminal half-life. Source. Adapted from Ref. 71. ... 

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