ONE COMPARTMENT OPEN MODEL
“The rate of change of drug amount in the body is the interplay between the rate of entry of drug into the system and the rate of its elimination or exit from the system”
In this the body is considered to a single uniform space into which the drug is administered, and from which it is eliminated; assuming that the administered drug immediately distributed throughout the space. The mathematical descriptors or pharmacokinetic parameters that are used to fully characterize the One Compartment Open Model are the
First order absorption rate constant (ka) that reflects the rate of entry into the compartment.
Bioavailability (F) that reflects the extent of drug entry into the compartment.
Apparent volume of distribution (Vd) that reflects the extent of drug distribution within the compartment.
Systemic clearance (Cl) the ability of the body to completely remove drug from a certain volume of blood or plasma per unit time and in concert with the drug concentration in the blood or plasma reflecting the rate of drug elimination from the system.
Elimination rate constant for the drug (Kel) calculated as [Cl/Vd] and the half-life (t1/2) calculated as [0.693/K] for the elimination of the drug are some of the derived parameters..
The extent of drug absorption may range from zero to the entire dose being absorbed depending on the fraction of the actual dose (F) that reaches the systemic circulation without being degraded, metabolized during absorption or lost unabsorbed.
The extent of distribution will be reflected by, Vd (ml), which is volume that can account for the relationship between the amount of drug in the body (mg) and the drug concentration observed (mg/ml) in plasma or blood, after distribution is complete. If distribution of drug is unequal with tissues taking up a lot of drug, the blood concentration observed for a certain amount of total drug in the compartment will be less. In contrast, if tissues show no tendency to take up and sequester a drug the concentration in the blood will be higher than in the previous case.
Most conventional drug delivery systems, for example tablets and capsules, are designed to release drug rapidly so as to enable quick and complete drug absorption. For these products, after drug release, the first order absorption process is also rapid. Since drug concentrations rise rapidly, the rate of elimination is also high. The overall result of the interplay between rapid absorption rate and subsequent elimination rate is a fairly steep bell shaped curve when drug concentrations are plotted with respect to time. A further consequence is that the time period for which drug concentration remains within the therapeutic window (i.e., duration of action) may be relatively short. This necessitates re-administration of further doses in order to sustain the clinical efficacy of the drug. This presents problems related to
(1) Compliance since the patient has now to take multiple doses, and
(2) Results in significant fluctuations in drug concentrations which may be undesirable in some cases.
1. Pharmacokinetics in Drug discovery and development by Ronald D. Schoenwald; Basic principles pg nos- 7-10
2. Integrated Pharmacology 2nd edition by Walker, Hoffmann,Curtis,Sutter,Clive; Pharmacokinetics pg nos- 50,51
to be continued.......
44. A drug is administered to a 65 kg patient as 500 mg tablets every 4 hours. Half life of the drug is 3 hrs, volume of distribution is 2 liter / kg and oral bioavailability of the drug is 0.85. calculate the steady state concentration of the drug ?
Continuation Of My Previous Blog........
iii) ALTERATION OF GASTRIC MOTILITY/RATE OF GASTRIC EMPTYING :
The pharmacokinetics of the antifungal pradimicin derivative BMS 181184 in plasma of normal, catheterized rabbits were characterized after single
97. Which of the followings parameters from the plasma concentration time profile study gives indication of the rate of drug absorption ?
The effect of type and concentration of vehicles on the dissolution rate of a poorly soluble drug (i
CONTINUATION OF MY PREVIOUS BLOG...........
ii) COMPLEXATION AND ADSORPTION :
a) TETRACYCLINE-METALS :
A patient was given a 160-mg dose of a drug IV, and 80 mg was eliminated during the first 120 minutes. If the drug follows first-order elimination kinetics, how much of the drug will remain 6 hours after its administration?
The main aim of chronokinetics studies is to control the time of administration which among others, can not only be responsible for verification of d