Blood drug concentration

Fig. 1. Blood—drug concentration curve used to determine bioavailabiLitv and bioequivalence. C is the maximum dmg concentration in the blood and corresponds to some The AUC (shaded) represents the total amount of orally adininistered dmg the time from points A to B represents dmg onset, from points B to D, the duration MEC = minimum effective concentration MTC = minimum toxic concentration and TI = therapeutic index.

Blood drug concentration and amount of drug in urine versus time data are usually sufficient to obtain parameters for Eq. (65). No doubt for many drugs this information is available in the literature, and independent studies may be unnecessary. Intrinsic organ clearance, CL, as presented in Eq. (26), is obtained from... 

A modification of the forcing function approach makes use of linear systems analysis for individual tissue compartments [59], Parametric or nonparamet-ric functions are fitted to observed blood drug concentration-time data and are then combined with tissue drug concentration-time measurements deconvolved... 

Thus, %F is defined as the area under the curve normalized for administered dose. Blood drug concentration is affected by the dynamics of dissolution, solubility, absorption, metabolism, distribution, and elimination. In addition to %F, other pharmacokinetic parameters are derived from the drug concentration versus time plots. These include the terms to describe the compound s absorption, distribution, metabolism and excretion, but they are dependent to some degree on the route of administration of the drug. For instance, if the drug is administered by the intravenous route it will undergo rapid distribution into the tissues, including those tissues that are responsible for its elimination. 

After oral administration of 400 mg of rifaximin to fasted healthy volunteers blood drug concentration was found to be lower than the detection limit of the analytical method (i.e. 2.5 ng/ml) in half of them [102]. In the remaining subjects very low amounts were detected at some of the time intervals during the first 4 h after intake. Along the same lines, the urinary concentrations of the drug were very low and often undetectable. The effect of food on the absorption of the antibiotic was also evaluated [34] and a significant, albeit not clinically relevant, increase of bioavailabity was observed after a high-fat breakfast (table 5). 

This information may affect selection criteria for the study population and the choice of tests in addition to routine safety monitoring, and will certainly determine the starting dose, range of doses, maximum exposure and dose increments to be studied. Pharmacokinetics in man may be quite different from those in animal species so that plasma and, if possible, tissue concentrations are generally more important than dose. One exception to this may be hepatotox-icity resulting from exposure of the liver to portal blood drug concentrations, when the oral dose administered to the animals may be more relevant than the systemic plasma concentrations, which reflect first-pass metabolism as well as absorption. 

While the study of the absorption, disposition, metabolism, and excretion of drugs, and their therapeutic applications falls properly within the province of the clinical pharmacologist, it is upon the skills and knowledge of the clinical biochemist that accurate, and hence clinically meaningful, measurements of blood drug concentrations depend. The clinical biochemist must therefore be familiar not only with the methodology, but also with the value, and limitations, of such measurements. 

A H SteadandA C Moffat, A Collection ofTherapeutic, Toxic and Fatal Blood Drug Concentrations in Man, Human Toxicol. 1983,3,437-464... 

Side effects are based on the dose and are noted 15-30 minutes after ingestion (peak 60 minutes) corresponding to blood drug concentration (sildenafil). Keep doses <100mg... 

Rapid absorption, often followed by rapid redistribution to tissue stores with consequent falls in brain and blood drug concentrations, plays a significant role in the quick onset and cessation of perceived effects, but longterm actions, for example mild sedative and antianxiety effects, are a consequence of slow hepatic clearance, either by hydroxylation and subsequent conjugation to a... 

The pharmacokinetics of thalidasine in a polyphase liposome preparation and in aqueous solution were determined by HPLC in mice following intravenous injection. The blood drug concentration curve fit a two-compartment open model, with the distribution and elimination half-lives being 3.52 and 23.58 minutes, respectively, for the liposome preparation, and 1.293 and 11.12 minutes, respectively, for the aqueous solution [149]. 

Given a zero time blood drug concentration (Co), a nonzero time concentration (Cf), and a defined time (t), then k can be readily determined either algebraically, graphically, or with appropriate software. For example, in a graphical plot of In Cf versus f, the slope of the linear relationship is k. The elimination rate constant k represents the fraction of drug removed per unit of time and has units of reciprocal time (min h" day" ). The overall elimination rate constant (k) includes the renal constant (fccR)> the biliary constant (fccs)) the metabolic constant (kcM)> and others such that k kcR "i kcB 3" kcM. 

Reduction in side effects associated with systemic toxicity, i.e. minimization of peaks and troughs in blood-drug concentration [7, 10]... 

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