Area under the concentration

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... 

Area under the concentration- inbloodstream vs. time curve... 

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. 

AUC, area under the concentration vs time curve N/A, not applicable. 

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. 

Figure 5.2 Plasma concentration curve of drug after single and repeated administration Csj. nax, maximal steady-state plasma concentration after repeated administration Css av, average steady-state concentration after repeated administration Css mm- minimal steady-state concentration after repeated administration n. maximal plasma concentration after single oral dose t Inax. time to maximal concentration after single oral dose t plasma half-life after single oral dose AUC, area under the concentration vs. time curve...

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. 

Blood samples were taken at 0.25, 0.5, 1.5, 2.5, 4.5, 6.5, 8.5, 10.5 and 12.5 h and the concentration of theophylline in serum was assayed by a spectrophotometric method [7]. The samples were analysed in duplicate. Bioavailability was calculated from the area under the concentration curve following the trapezoidal rule. 

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... 

Tiagabine is 90-100% bioavailable, has linear kinetics, and is highly protein-bound. The half-life is 5-8 hours and decreases in the presence of enzyme-inducing drugs. Food decreases the peak plasma concentration but not the area under the concentration curve (see Chapter 3). Hepatic impairment causes a slight decrease in clearance (and may necessitate a lower dose), but the drug does not cause inhibition or induction of hepatic... 

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. 

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