Pharmacokinetics one-compartment

Fit the amount of 3,5,6-TCP excreted in individual urine samples to a one-compartment pharmacokinetic model that describes the time course of 3,5,6-TCP in urine of volunteers following the application of chlorpyrifos to the forearm (72% of dose excreted).3... 

McCarley K, Bunge AL (1998) Physiologically relevant one-compartment pharmacokinetic models for skin. 1. Development of models. J Pharm Sci 87 470-481. 

This approach assumes that the blood clearance profile of the dye follows an open one-compartment pharmacokinetics model. The characteristics of such a... 

A study we performed with mini pigs in cooperation with the University of Zurich30 showed, after intravenous administration, that the derivatives of protopanaxatriol, as Rglr have a one compartment pharmacokinetic profile, and a half-life of about 30 min. Whereas for the derivatives of protopanaxadiol, such as Rbj, the half-life is much longer, about 16 h, and its pharmacokinetics is described with a two-compartment model (Figure 16.30). 

FIGURE 4-4 Influence of biologic half-life relationship between exposure level (E, upper left) and biomarker level (BM). Daily exposure levels were created by Monte Carlo sampling from auto-correlated lognormal distribution. Observation time is 400 days. Biomarker levels were calculated for three half-lives—1 day (upper right), 1 month (lower left), and 1 year (lower right)—with one-compartment pharmacokinetic model. 

Stern, A.H. 1997. Estimation of the interindividual variability in the one-compartment pharmacokinetic model for methylmercury Implications for the derivation of a reference dose. Regul. Toxicol. Pharmacol. 25(3) 277-288. 

Case Example of Use of One-Compartment Pharmacokinetic Model to Estimate Intake Dose of Slowly Cleared Lipid-Soluble Chemicals 2,3,7,8-TCDD... 

The value of AUC (O-oo) may also be expressed as given in Eq. (4) for a drug whose disposition in the body can be described by a one-compartment pharmacokinetic model. 

It is often possible to manipulate the mathematical model into the form of a straight-line equation. For example, the one compartment pharmacokinetic model after an IV bolus can be expressed as a differential equation or as an exponential equation as shown earlier. By taking the natural log of the exponential equation, Eq. (17) in the form of a straight line can be derived ... 

Even though the absorption rate constant (kf) defines the rate of absorption, its accurate determination is largely dependent on the adequacy of the plasma concentration-time data associated with the absorption phase of the drug. When a drug is administered orally, as a conventional (immediate-release) dosage form, or injected intramuscularly as an aqueous parenteral solution, the absorption and disposition kinetics can often be analysed in terms of a one-compartment pharmacokinetic model with apparent first-order absorption. The plasma concentration-time curve is described by the equation... 

Unlike the estimates of dosage rates and average steady-state plasma concentrations, which may be determined independently of any pharmacokinetic model in that systemic clearance is the only pharmacokinetic parameter used, the prediction of peak and trough steady-state concentrations requires pharmacokinetic compartmental model assumptions. It is assumed that, (i) drug disposition can be adequately described by a one-compartment pharmacokinetic model, (ii) disposition is independent of dose (i.e. linear pharmacokinetics apply), and (iii) the absorption rate is much faster than the rate of elimination of the drug, which is always valid when the drug is administered intravenously. For clinical applications, these assumptions are reasonable. 

D. Soy, S. L. Beal, and L. B. Sheiner, Population one-compartment pharmacokinetic analysis with missing dosage data. Clin Pharmacol Ther 76 441 51 (2004). 

A new molecular entity exhibiting one-compartment pharmacokinetics with first-order absorption was assumed. The typical (mean) values of the population PK parameters for the NME were 1 h 17.5L/h, and SOL for absorption rate constant (Ka), apparent clearance (CLIP), and apparent volume of distribution (V/F), respectively. An intersubject variability of 45% (coefficient of variation) was assumed for each of these parameters, and this was assumed to be lognormally distributed with a mean of zero. A proportional error model was assumed for the residual error of 15%. 

HI-6 was administrated to rats in dose 36,0 mg/kg b.w. ( l,0xl0-4 M/kg b.w.), Diazepam - 2,5 mg/kg and Scopolamine - 0,5 mg/kg, b.w. administrated i.m. Rats intoxicated with 1,5 LD50 soman (70 pg/b.w., i.m.) were treated 1 min later with drug combination. A HPLC-method for analysis of HI-6 was used. Time-related plasma concentrations were fitted to one-compartment pharmacokinetic model. The result of plasma concentrations are presented in Figure 8 and pharmacokinetics parameters on Table 7. 

Required Rate of Release. Controlled-release delivery systems are an alternative to frequent intravenous administration. Here, we consider the design of an implantable controlled-release matrix for T-20 delivery to human patients. The objective is to provide sustained plasma levels after a single administration. A one-compartment pharmacokinetic model provides a useful means for estimating the required rate of release from the matrix. Equation 7-1 can be modified to account for a continuous release of drug into the central compartment ... 

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