Pharmacokinetics Language English Format: PDF Price - Tutorsindia

PharmacokineticsDistribution: Compartments and Volume of DistributionIt was stated earlier that the intended physical meaning of the volume of distribution was that it should reflect the extentof drug distribution out of the blood into the tissues. Figure 3.13 shows that V does indeed reflect that property.--In (a) most of the drug stays in the blood, leaving a high blood concentration. When we calculate V = D/Cwe obtain a small volume. We thus achieve the relationship we wanted – a low tendency for drug to movefrom the blood into the tissues is associated with a small value for V.--In (b) more of the drug has moved from the blood – this leaves a lower concentration – the calculated valueof V is greater.--In (c) there is very extensive movement – little drug remains in the blood – calculated V is appropriatelylarge, reflecting the degree of movement into the tissues.(a)BloodTissuesStays mainly in blood.Blood concentration high.V = D/C small vol dist(b)Distributes evenly.Moderate blood concentration.V = D/C medium vol dist(c)Distributes strongly into tissue.Low blood concentration.V = D/C large vol distFigure 3.13 The volume of distribution reflects the extent of drug movement out of the blood into tissuesTable 3.2 shows the average volume of distribution in a 70kg adult for a range of drugs which have been selected toillustrate the wide range of values that can arise.Substance Volume of distribution (L) Broad classAdalimumab 5Warfarin 7Small: Mainly retained in the blood.Gentamicin 16Theophylline 35 Medium: Distributed fairly evenly betweenCimetidine 140blood and tissues.Digoxin 510Doxepin 1,600Chloroquine 15,000Large: Majority of drug moves outof blood into the tissues.Table 3.2 Volumes of distribution of substances with widely varying characteristics.The three substances with small volumes are retained in the blood for differing reasons. Adalimumab is a monoclonalantibody (a protein with a molecular weight well over 100,000) that is virtually restricted to the plasma compartment.Warfarin binds tightly to serum albumin which prevents it from distributing and gentamicin is a very water solubleantibiotic with limited distribution and very little penetration into cells.34Download free ebooks at bookboon.com