Pharmacokinetics drug distribution within body

Pharmacokinetics relates to the fate of a drug in the body, particularly its ADME, i.e. its absorption into the body, its distribution within the body, its metabolism by the body, and its excretion from the body. 

Quinine is derived from the bark of the cinchona tree, a traditional remedy for intermittent fevers from South America. The alkaloid quinine was purified from the bark in 1820, and it has been used in the treatment and prevention of malaria since that time. Quinidine, the dextrorotatory stereoisomer of quinine, is at least as effective as parenteral quinine in the treatment of severe falciparum malaria. After oral administration, quinine is rapidly absorbed, reaches peak plasma levels in 1-3 hours, and is widely distributed in body tissues. The use of a loading dose in severe malaria allows the achievement of peak levels within a few hours. The pharmacokinetics of quinine varies among populations. Individuals with malaria develop higher plasma levels of the drug than healthy controls, but toxicity is not increased, apparently because of increased protein binding. The half-life of quinine also is longer in those with severe malaria (18 hours) than in healthy controls (11 hours). Quinidine has a shorter half-life than quinine, mostly as a result of decreased protein binding. Quinine is primarily metabolized in the liver and excreted in the urine. 

Azaperone is a widely used sedative drug in pigs. Available pharmacokinetic studies are insufficient to determine the extent of absorption of azaperone from the gastrointestinal tract. However, by comparison with the excretion profile following parenteral dosing, absorption after oral dosing is probably high. Distribution within the body of rats was extensive, and excretion was primarily in the feces (81%), with lesser amounts in urine (16%) (104). 

FIGURE 30.2 Two-compartment model for peritoneal pharmacokinetics. Drug administered via a catheter is placed in the peritoneal cavity with a distribution volume of VpQ, yielding concentrations within the peritoneum of Cpc- Subsequent transfer betw een the peritoneum and the body compartment is mediated by diffusion with a permeability coefficient—surface area product of PA. CLp is the elimination clearance from the body. Plasma drug concentrations (Cp ) and systemic toxicity are minimized because the distribution volume of the body compartment (Vd) is much greater than VpQ and because CLp prevents complete equilibration of concentrations in the tw o compartments. (Adapted from Dedrick RL et al. Cancer Treat Rep 1978 62 1-11.)... 

Pharmacokinetics is concerned with the rate at which drug molecules cross cell membranes to enter the body, to distribute within it and to leave the body, as well as with the structural changes (metabolism) to which they are subject within it. 

A. Phase I trials normally involve a small number of volunteers who are not suffering from the medical condition the new entity is intended to treat. (Note that in some disease areas such as oncology, even Phase I trials are often conducted using patients as subjects, due to the adverse experiences caused by some new therapies.) One intention of these studies is to determine the nature and speed with which the new drug is distributed within the body, and then in what way and how quickly it is eliminated. This is the discipline of pharmacokinetics. Another is to determine the highest dose in man that is consistent with an acceptable level of adverse experiences. 

Pharmacokinetics refers to activities within the body after a dmg is administered. These activities include absoqrtion, distribution, metabolism, and excretion (ADME). Another pharmacokinetic component is the half-life of the drug. Half-life is a measure of the rate at which drains are removed from the body. 

The success of treating tumours, especially solid tumours, by systemic therapy depends on various characteristics of the tumour. Besides the importance of intrinsic drug activity and the potential targets within the tumour cells, drug pharmacokinetics and whole body distribution, site of delivery and the ability of site-specific targeting (affinity) are important features. 

The concentration (c) of a solution corresponds to the amount (D) of substance dissolved in a volume (V) thus, c = D/V. If the dose of drug (D) and its plasma concentration (c) are known, a volume of distribution (V) can be calculated from V = D/c. However, this represents an apparent volume of distribution (Vapp), because an even distribution in the body is assumed in its calculation. Homogeneous distribution will not occur if drugs are bound to cell membranes (5) or to membranes of intracellular organelles (6) or are stored within the latter (7). In these cases, Vapp can exceed the actual size of the available fluid volume. The significance of Vapp as a pharmacokinetic parameter is discussed on p. 44. 

Pharmacokinetic studies in pigs following a single oral administration of 20 mg kitasamycin/kg bw showed that the drug was rapidly absorbed and distributed in the body. A maximum plasma concentration of 4.5 ppm was attained within 0.5 h, the half-life in plasma being 0.7 h. Highest tissue residue concentrations (21 ppm) were detected in kidney within 1-2 h. The ratio of the maximum concentrations determined in kidney to that in liver was around 3 2. 

The pharmacokinetic properties of the benzodiazepines in part determine their clinical use. In general, the drugs are well absorbed, widely distributed, and extensively metabolized, with many active metabolites. The rate of distribution of benzodiazepines within the body is different from that of other antiseizure drugs. Diazepam and lorazepam in particular are rapidly and extensively distributed to the tissues, with volumes of distribution between 1 L/kg and 3 L/kg. The onset of action is very rapid. Total body clearances of the parent drug and its metabolites are low, corresponding to half-lives of 20-40 hours. 

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