Distribution is the process by which drug molecules transfer between the circulating blood, interstitial space and intracellular fluid. This is influenced by the drug’s molecular size and lipid solubility, the extent to which it binds to proteins in plasma, its susceptibility to drug transporters expressed on cell surfaces and its binding to its molecular target and to other cellular proteins (which can be irreversible). Most drugs diffuse passively across capillary walls down a concentration gradient into the interstitial fluid until the concentration of free drug molecules in the interstitial fluid is equal to that in the plasma. As drug molecules in the blood are removed by metabolism or excretion, the plasma concentration falls and drug molecules diffuse back from the tissue compartment into the blood until eventually all are eliminated. Note that this reverse movement of drug away from the tissues will be prevented if further drug doses are administered and absorbed into the plasma.

Volume of distribution

The apparent volume of distribution (V_d ) is the volume into which a drug appears to have distributed following intravenous injection. It is calculated from the equation

V_d = D.C₀

where D is the amount of drug given and C₀ is the initial plasma concentration (Fig. 1). Drugs that are highly bound to plasma proteins may have a V_d below 10 L (e.g. warfarin, aspirin), while those that diffuse into the interstitial fluid but do not enter cells because they have low lipid solubility may have a V_d between 10 and 30 L (e.g. gentamicin, amoxicillin). It is an ‘apparent’ volume because those drugs that are lipid-soluble and highly tissue-bound may have a V_d of greater than 100 L (e.g. digoxin, d amitriptyline). Drugs with a larger V_d have longer half-lives , take longer to reach steady state on repeated administration and are eliminated more slowly from the body following discontinuation.

Fig1. Drug concentrations in plasma following single and multiple drug dosing. In this example of first-order kinetics following a single intravenous dose, the time period required for the plasma drug concentration to halve (half-life, t,,) remains constant throughout the elimination process.

مواضيع ذات صلة

Drug elimination

Dose–response relationships

السلفوناميدات

Antibiotic Resistance

البنسيلينات Penicillins

المضادات الحيوية المثبطة لصناعة الجدار الخلوي

Aminoglycosides and spectinomycin

β-lactam antibiotics

مضادّات الببتيد الدهنية وغليكو ببتيد الدهنية الحيوية

التجميع الإنزيمي للبتيد السباعي للفانكوميسين وكلوروإرموميسين (chloroermomycin)

تعديلات السلسلة الجانبية في مضادّات الكيفالوسبورين: أجيال متعددة

Drug targets and mechanisms of action