Area-under-the-blood-concentration

The answer is e. (Hardman, p 21J The fraction of a drug dose absorbed after oral administration is affected by a wide variety of factors that can strongly influence the peak blood levels and the time to peak blood concentration. The Vd and the total body clearance (Vd x first-order fte) also are important in determining the amount of drug that reaches the target tissue. Only the area under the blood concentration-time curve, however, reflects absorption, distribution, metabolism, and excretion factors it is the most reliable and popular method of evaluating bioavailability... 

AUC—area under the (blood concentration-time) curve AV—atr io ven t r icu lar p—beta... 

Area under the curve (AUC) The area-under-the-blood-concentration-time curve reflects the amount of a xenobiotic that has effectively reached the systemic circulation and as such is influenced both by the degree of bioavailability and by the rate at which a chemical is removed from the body. AUC is a good indicator of the internal exposure dose in the body since it takes into consideration not only the blood concentration of a xenobiotic but also the time a xenobiotic is present in the blood compartment and thus in the body. 

Although other measures of chronic dose may be more appropriate for predicting the hazard posed by specific chronic or carcinogenic toxicants, such as an area-under-the-blood-concentration (AUC) curve or the peak target tissue concentration, the LADD is the most common dose metric used in carcinogen risk assessment (Paustenbach and Madl 2008). 

AUC area under the blood/plasma/serum concentration-time... 

Figure 2.4. In vivo measurement of blood-brain barrier (BBB) permeability, (a) Internal carotid artery perfusion technique (i) in the rat. Other branches of the carotid artery are ligated or electrically coagulated (o, occipital artery p, pterygopalatine artery). The external carotid artery (e) is cannulated and the common carotid artery (c) ligated. Perfusion time may range from 15 s to 10 min, depending on the test substance. It is necessary to subtract the intravascular volume, Vo, from (apparent volume of distribution), to obtain true uptake values and this may be achieved by inclusion of a vascular marker in the perfusate, for example labelled albumin. Time-dependent analysis of results in estimates of the unidirectional brain influx constant Ki (pi min which is equivalent within certain constraints to the PS product. BBB permeability surface area product PS can be calculated from the increase in the apparent volume of distribution Vd over time. Capillary depletion, i.e. separation of the vascular elements from the homogenate by density centrifugation, can discriminate capillary uptake from transcytosis. (b) i.v. bolus kinetics. The PS product is calculated from the brain concentration at the sampling time, T, and the area under the plasma concentration-time curve, AUC.

AUC Area Under the (blood/plasma concentration versus time) Curve... 

The extent of absorption of a drug can be estimated by comparing the total area under the drug concentration in the blood versus time curve or the total amount of unchanged drug excreted in the urine after administration of drug and compared to the administration of standard (standard may be an intravenous injection, where the bioavailability of a drug reaches 100%). 

It has been shown that coadministration of a single dose of diltiazem with rapamycin leads to higher rapamycin exposure, The mean whole blood rapamycin area under the plasma concentration in time curve increased by 60% and the maximum concentration increased by 43%. Coadministration also decreased the renal clearance of rapamycin, presumably by inhibiting the first-pass metabolism of rapamycin (12). 

Establishing clinical bioequivalence to a reference delivery method, usually a needle and syringe or an autoinjector or pen injector is the customary method of demonstrating that these conditions have been successfully met. This requires that the maximum blood plasma concentration of the drug (Cmax) and the total area under the time-concentration curve (AUC), as well as their associated confidence intervals, adequately approximate a reference product. The standard criteria to establish bioequivalence are 70-143% for Cmax and 80-125% for AUC (Fig. 3 for an example of a bioequivalent needle-free delivery). 

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