Pharmacokinetics: An IntroductionI. Volume of Distribution.- II. Compartments.- 1. Protein Binding.- 2. Gastrointestinal Reabsorption.- III. Elimination.- 1. Equation for Elimination.- a) Theoretical Initial Concentration.- b) Half-Time of Elimination.- c) Rate Constant of Elimination.- d) Total Clearance.- e) Saturation Kinetics.- f) Determination of Pharmacokinetic Data from Urine.- IV. Steady State.- 1. Conditions for a Steady State.- a) The Exchangeable Pool.- b) Experimental Analysis of a Natural Steady State.- c) Endogenous Transfer.- 2. Artificial Steady State - Continous Infusion.- V. Multicompartment Systems.- 1. The Model.- a) Invasion.- b) Concentration-Time Curve for Simultaneous Invasion and Elimination.- c) The Bateman Function.- 2. Dost's Principle of Corresponding Areas.- a) Test of Completeness of Invasion.- b) Rule of Corresponding Areas as a Supplement to the Basic Pharmacokinetic Experiment.- 3. Dost's Rule of Corresponding Fractional Areas.- a) Fractional Quantities and Fractional Areas.- b) Conversion of Areas to Quantities of Substance.- 4. General Consideration of Multicompartment Models.- a) Multi-Exponential Function.- b) Subdivision into Individual e-Functions.- c) Practical Importance of the C; y-Expression.- VI. Pharmacokinetics and Treatment.- 1. Repeated Administration of a Drug.- a) Duration of Accumulation.- b) Degree of Accumulation.- VII. Pharmacokinetics of Gastrointestinal Absorption.- 1. Gastrointestinal Absorption and the Bateman Function.- 2. Reconstruction of the Invasion Curves.- 3. Use of the Invasion Curves.- 4. Calculation of Dose-Proportional Absorption.- 5. Variants of the Invasion Process in Gastrointestinal Absorption.- a) Variants in the Site of Absorption.- b) Delay in Invasion Due to Lymphatic Transport of Lipid-Soluble Substances.- c) Physical and Chemical Reactions After Absorption.- d) Excretion and Reabsorption of Substances in the Intestine.- e) Limitation of the Absorptive Capacity.- f) Different Absorptive Capacity of Two Segments of Intestine.- 6. Conclusions.- 7. Appendix: Some Formulae and Their Derivation.- VIII. Interaction.- 1 Elimination.- a) Pathological Changes in the Organ of Excretion.- b) Age-Dependent Changes in Elimination.- c) Pharmacogenetic Factors.- d) Dependence of Rate of Elimination on Acid-Base Balance.- e) Circadian Rhythm of Excretion Rate.- f) Water Diuresis and Rate of Elimination.- g) Solvent Deficiency.- h) Enzyme Induction.- i) Inhibition of Elimination by Toxicity.- 2. Volume of Distribution.- a) Hydration and Dehydration.- b) Hydropic States.- 3. Conclusions.- IX. Use of Analogue Computers in Pharmacokinetics.- 1. Principle of the Analogue Computer.- 2. Programming the Analogue Computer.- 3. Use.- X. Practical Application of Pharmacokinetic Procedures.- 1. Methods of Measurement.- a) Microbiological Methods.- b) Chemical Analysis.- c) Radioactively Labelled Substances.- 2. Assessment of the Results of Animal Experiments.- 3. Derivation of Pharmacokinetic Parameters and Constants.- a) Calculation from a Graph.- b) Programmend Procedures.- 4. Mathematical Basis of Programming.- a) Distribution of a Substance Between Several Compartments.- b) Blood Concentration-Time Curves for Pure Invasion.- c) Blood Concentration-Time Curves for Pure Elimination.- d) Blood Concentration-Time Curves for Simultaneous Invasion and Elimination (Batemann Function).- e) Accumulation, Limiting Curve.- f) Dosage Scheme.- 5. Examples of Calculation.- Further Reading. |
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Volume of Distribution | 1 |
Gastrointestinal Reabsorption | 8 |
Steady State | 22 |
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Abscissa analogue computer analogue computer programme ascorbic acid Bateman function bilirubin blood concentration blood concentration-time curve body calculated chloramphenicol chyme Coefficient of distribution compartment concentration curve constant of elimination continuous infusion corresponding depot determined differential equations digital computer dosage dose-interval Dost drug e-functions effect elimination constant endogenous enzyme example excretion experiment experimental exponential function extracellular fluid fraction gastrointestinal absorption given graph half-time of elimination injection input integral intestinal intramuscular intravenous administration invasion and elimination invasion constant invasion curve k₁ k₁ and k₂ k₁-k₂ k₂ kinetics linear liver logarithmic mathematical measured methods mg/kg mg/litre neonates obtained Ordinate pharmacokinetic pharmacokinetic model phase phenobarbitone phenylbutazone plasma plotted potentiometer procedure processes pure elimination radioactive rate constant rate of elimination semilogarithmic serum shows steady straight line sulphonamides t₁ t₂ Table test substance theoretical initial concentration total clearance urine volume of distribution y₁ ymin дуо