Blood plasma concentration

Piel et al. compared the intravenous pharmacokinetics of miconazole in sheep after its administration in a polyoxyl-35 castor oil/lactic acid mixture, a 100 pM hydroxylpropyl-/l-cyclodextrin-50 pM lactic acid solution, and a 50 pM sulfobutyl ether (SBE7)-/i-cyclodextrin 50 pM lactic acid solution. Intravenous administration of 4 mg/kg of miconazole was completed within 5 min [108]. There were no differences of the miconazole blood plasma concentration versus time for the three dosage forms. The half-life of distribution was <2.4 min. Both hydroxylpropyl-/ -... 

Lethal. At time of respiratory arrest, blood plasma concentration was 1.0 mg total CN/L or about 0.4 mg free cyanide/L No measurable effect on food consumption, blood chemistry, behavior, or organ histology... 

In order to obtain an in vitro-in vivo relationship two sets of data are needed. The first set is the in vivo data, usually entire blood/plasma concentration profiles or a pharmacokinetic metric derived from plasma concentration profile (e.g., cmax, tmax, AUC, % absorbed). The second data set is the in vitro data (e.g., drug release using an appropriate dissolution test). A mathematical model describing the relationship between these data sets is then developed. Fairly obvious, the in vivo data are fixed. However, the in vitro drug-release profile is often adjusted by changing the dissolution testing conditions to determine which match the computed in vivo-release profiles the best, i.e., results in the highest correlation coefficient. 

Van den Bosch JMM, Westermann CJJ, Aumann J, Edsbacker S, Tonneson M, Selroos O (1993) Relationship between lung tissue and blood plasma concentrations of inhaled budesonide. Biopharm Drug Dispos 14 455 159. 

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

II.a.3. Repeated Oral Dosing with Measurements of Blood Plasma Concentration over Time... 

Partitioning of some drugs into cells occurs. Red blood cells parasitized by malaria selectively take up chloroquine, which accounts in part for the efficacy of this antimalarial against intracellular malarial forms. The intrahepatocellular concentration of chloroquine is 500 times that of the blood plasma concentration. Macrolides and fluoroquinolones are also selectively partitioned into cells, which accounts in part for their efficacy against mycoplasma and chlamydia, both intracellular pathogens. 

Figure 8 (A) In vitro permeability of candidate drug molecules in the presence of synergistic combinations of penetration enhancers (SCOPE) formulations. Open circles indicate passive skin permeability and closed circles indicate skin permeability in the presence of SCOPE formulations as a function of the molecular weight of the solute. (B) In vivo delivery of leuprolide acetate, a synthetic analogue of LHRH in hairless rat model, y-axis shows blood plasma concentration of leuprolide acetate as a function of time for control formulation (open circles) and SCOPE formulation (closed circles). Abbreviation-. LHRH, luteinizing hormone-releasing hormone.

Plasma versus Blood Clearance Calculation of Eh from drug clearance in blood requires the determination of chug concentration in whole blood. Since the determination of chug concentration is usually performed in plasma or serum, knowledge of the blood/plasma concentration ratio is necessary to estimate the blood clearance. Blood clearance is calculated using the equation... 

Fig. 11 Great Lakes food web, with approximate PCB concentrations. Note that PCB concentrations vary significantly among species in different locations, and among individuals of the same species. Concentrations in humans are estimated from the blood plasma concentrations in humans that eat Lake Michigan fish [314] and the distribution of PCBs in the body of rats [35]. See text for additional references...

It is relevant to ask how often the routine measurement procedures currently used in laboratory medicine provide results that are traceable to high-level calibrators and reference measurement procedures (Lequin personal communication). It turns out that primary reference measurement procedures and primary calibrators are only available for about 30 types of quantity such as blood plasma concentration of bilirubins, cholesterols and sodium ion. International reference measurement procedures from the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and corresponding certified reference material from BCR are available for the catalytic activity concentration of a few enzymes such as alkaline phosphatase and creatine kinase in plasma. For another 25 types of quantity, such... 

FIGURE 2 (a) Schematic picture of blood plasma concentration profile after administra-... 

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). 

Yuan, J.H. Modeling blood/plasma concentrations in dosed feed and dosed drinking water toxicology studies. Toxicol Appl Pharmacol 119 131-141, 1993. 

In fact, other studies have now shown that IV vitamin C gives much higher blood concentrations than oral dosages, and blood plasma concentrations are 60 times higher. Although clinical trials are always difficult to set up, some have been under way at the University of Kansas Medical Center, under the direction of Jeanne... 

Lumped parameter models for tissues are also referred to as compart-mental or pharmacokinetic models. These models can be divided into two categories—classical and physiological (or whole-body) compartmental analyses. In the classical approach, the body or a region of body is represented by one or more compartments, without relating the content or inputs or outputs associated with these compartments to available physiological and physicochemical information. These models are useful when it is sufficient to know and to be able to control the blood (plasma) concentration, and the details of any distribution in various tissues are not necessary (for details on classical pharmacokinetics, see Wagner, 1971). 

Establish blood/plasma concentration-time profiles and derivation of key pharmacokinetic parameters and variables... 

A person ingests a morphine overdose. The half-life of morphine in blood is about 3.0 h. If the blood plasma concentration 5.0 h after ingestion was 6.0 mg dm of blood, estimate the peak concentration of morphine at the time of ingestion. 

Exposure assessment studies have concluded that both food and drinking water can be major exposure pathways to humans [16, 76]. It was also shown that contaminated drinking water yields higher blood plasma concentrations of PFOA in humans [77-79]. The consumption of drinking water was estimated to give <0.5% and 16% of the total human exposure to PFOS and PFOA, respectively [80]. However, data used for this assessment were limited in the concentrations of specific dietary items available for the assessment. 

Tybor, P.T., Dill, C.W. and Landmann, W.A. (1973) Effect of decolorisation and lactose incorporation on the emulsification capacity of spray-dried blood plasma concentrates. J. Food Sci. 38, 4. 

Maximum blood plasma concentration Area under plasma concentration-time curve Renal clearance Half-life... 

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