Pharmacokinetic Aspects of Psychopharmacology

There are two further terms which are important in pharmacokinetics -the clearance and the volume of distribution. The volume of distribution (Vj) relates the quantity of drug in the body to that in the blood or plasma. This 

Fundamentals of Psychopharmacology. Third Edition. By Brian E. Leonard 2003 John Wiley Sons, Ltd. ISBN 0 471 52178 7 

The clearance of a drug is usually defined as the rate of elimination of a compound in the urine relative to its concentration in the blood. In practice, the clearance value of a drug is usually determined for the kidney, liver, blood or any other tissue, and the total systemic clearance calculated from the sum of the clearance values for the individual tissues. For most drugs clearance is constant over the therapeutic range, so that the rate of drug elimination is directly proportional to the blood concentration. Some drugs, for example phenytoin, exhibit saturable or dose-dependent elimination so that the clearance will not be directly related to the plasma concentration in all cases. 

Once the clearance rate for a drug is known, the frequency of dosing may be calculated. It is usually desirable to maintain drug concentrations at a steady-state level within a known therapeutic range. This will be achieved when the rate of drug administration equals the total rate of clearance. 

Another term which is important in pharmacokinetics is the half-life (fi/2) of a drug. This value is related to the Vd and the total clearance. If it is assumed that the body is a single compartment in which the size of the compartment equals the Vd, the fi/2 may be calculated from the equation  

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Cone EJ (1995) Pharmacokinetics and pharmacodynamics of cocaine, J Anal Toxicol 19 459-78 Cryan JF, Bruijnzeel AW, Skjei KL, Markou A (2003) Bupropion enhances brain reward function and reverses the affective and somatic aspects of nicotine withdrawal in the rat. Psychopharmacology 168 347-358... 

Quantitative Applications - The use of stable-isotope-labeled compounds as internal standards for the quantitation of drugs and metabolites in biological fluids offers a unique combination of sensitivity and selectivity of detection for pharmacokinetic studies. The principles of the technique have been outlined, and applications up to 1981 have been compiled. Specific aspects of the isotope dilution method, e.g. its utility as a reference technique and associated procedures for handling the data generated from the use of multiple isotope tracers simultaneously, have been discussed. Examples of isotope dilution methods used in clinical psychopharmacology have also been reviewed. ... 

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