Drug concentration calculation

Ideal for studying the dose-response relationship for QT interval prolongation taking into account all the pharmacological properties of a compound The dog model is one of the most widely used anesthetized rabbits (especially female rabbits) have also been proposed for high sensitivity It provides complementary information with respect to in vitro tests (activity of metabolites, measurement of plasma drug concentrations, calculation of the volume of distribution) Possibility to induce experimental TdP... 

Specified experimental conditions (e.g., pH, stirring, drug concentration, Papp calculation). 

A study of the potency of the antibiotic daptomycin cited plasma protein binding of 92%, but it claimed only a 2-fold shift in potency in serum (expected 12-fold) [68]. This type of discrepancy is relatively common and can often reflect substantial binding to components in the "serum-free" media. In the cases of HIV-directed non-nucleotide reverse transcriptase inhibitors, this has been dealt with by measuring the unbound drug concentration in the "serum-free" medium and using that data to calculate the intrinsic, serum-free potency [69]. 

Use of proportion is very common in dosage calculations, especially in finding out the drug concentration per teaspoonful or in the preparation of bulk or stock solutions of certain medications. In a given proportion, when any three terms are known, the missing term can be determined. Thus, for example, if a/b = c/d, then ... 

The regression equation, calculated from the standard solutions in each collection, is employed to determine quantitatively the drug concentration present in individual plasma samples. 

To be able to calculate the Fabs using Eq. 9, the concentration profile in the intestine has to be understood. Sinko et al. [45] considered three different cases covering conditions where the inlet and outlet drug concentrations are below the saturation solubility (Cs) of the drug in the intestinal fluids, where the drug inlet and outlet concentrations are above Cs (i.e., solid drug exists throughout the intestine), and the intermediate situation where the inlet concentration is above but the outlet concentration below Cs. 

The main input parameter used to define the highest possible drug concentration in the intestine and to calculate the dissolution rate in the GI tract is the solubility of the dmg in the GI fluids. As described earlier (Sect. 21.2) there are several, both physiological and physicochemical, factors that can affect the solubility in the GI tract and it is therefore important to consider the relevance of the solubility data generated in the early drug discovery phase. A common approach is to use in silico models to predict the solubility of drugs (e.g., [5]). The advantage of this approach is that only the chemical... 

The haif-iife of a drug is the amount of time it takes to reduce concentrations by 50%. With each successive half-life duration, drug concentrations are further reduced until it is no longer present (figure 3.2). In a one-compartment model, a single half-life may be sufficient, but in multiple-compartment models, more than one half-life may need to be calculated. Half-life varies as a function of both the volume of distribu-... 

Once the clearance rate for a drug is known, the frequency of dosing may be calculated. It is usually desirable to maintain drug concentrations at a steady-state level within a known therapeutic range. This will be achieved when the rate of drug administration equals the total rate of clearance. 

The Drug Delivery Index (DDI) ahows a quantification of the reduction in the drug dose and the systemic exposure observed after drug release specificahy to the colon [37]. It may be calculated using AUC (Area l/nder the plasma drug concentration-time Curve) data or drug concentrations in blood and colonic tissues under steady-state conditions ... 

PK models (Section 13.2.4), PD models (Section 13.2.5), and PK/PD models (Section 13.2.6) can be used in two different ways, that is, in simulations (Section 13.2.7) and in data analysis (Section 13.2.8). Simulations can be performed if the model structure and its underlying parameter values are known. In fact, for any arbitrary dose or dosing schedule the drug concentration profile in each part of the model can be calculated. The quantitative measures of the effectiveness of drug targeting (Section 13.4) can also be evaluated. If actual measurements have been performed in in-vivo experiments in laboratory animals or man, the relevant model structure and its parameter values can be assessed by analysis of plasma disappearance curves, excretion rate profiles, tissue concentration data, and so forth (Section 13.2.8). 

If an appropriate model is selected and the model parameters are known, the time course of the drug concentration in each compartment (PK models) and the drug effect (PK/PD models) can be calculated for any dosing regimen. In addition, the relevant measures of the effectiveness of drug targeting can be calculated (see Section 13.4). 

The volume of distribution is a parameter that can be calculated from plasma drug concentration versus time data (expressed as area under the curve or AUC), according to the two equations shown below, for terminal or steady-state volume of distribution, respectively. 

How can you calculate the dose to achieve this concentration Remember the experiments above in which an apparent volume of distribution of a drug was calculated by giving a known amount intravenously (i.e., 100% bioavailability), and measuring the plasma concentration at various time points afterwards (Fig. 6). 

Poorly perfused tissues (adipose tissue, connective tissue, and bone) require hours to come into equilibrium with plasma drug concentrations (Fig. 25.1). Since the accumulation of anesthetic in body fat is relatively small soon after its IV administration, it is common clinical practice to calculate drug dosage on the basis of lean body mass rather than on total body weight. Thus, an obese patient may receive the same dose of IV anesthetic as a patient of normal body weight. 

Talwar et al. reported a simultaneous spectrophotometric determination of diloxanide furoate and metronidazole in dosage forms [15]. The drug substances were extracted from tablets with methanol, and the extract diluted with 0.01 M sodium hydroxide. The absorbance of the solution was measured at 247 and 320 nm against 0.01 M sodium hydroxide, and the concentration of each individual drug was calculated by the Vierordt method. Drug recoveries were in the range of 99 to 100%, and the method was satisfactorily applied to the analysis of commercial samples. 

Clearance (Cl) and volumes of distribution (VD) are fundamental concepts in pharmacokinetics. Clearance is defined as the volume of plasma or blood cleared of the drug per unit time, and has the dimensions of volume per unit time (e.g. mL-min-1 or L-h-1). An alternative, and theoretically more useful, definition is the rate of drug elimination per unit drug concentration, and equals the product of the elimination constant and the volume of the compartment. The clearance from the central compartment is thus VVklO. Since e0=l, at t=0 equation 1 reduces to C(0)=A+B+C, which is the initial concentration in VI. Hence, Vl=Dose/(A+B-i-C). The clearance between compartments in one direction must equal the clearance in the reverse direction, i.e. Vl.K12=V2-k21 and VVkl3=V3-k31. This enables us to calculate V2 and V3. 

---