Pharmacology in Clinical Practice by Richard Lancaster (Auth.)

By Richard Lancaster (Auth.)

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E. an appropriate dose interval would be 8 hours. 3. If the t| does not vary with changes in plasma concentration, then plasma log drug concentration vs. time plots are parallel when plotted starting from different plasma concentrations. 16 8 Log plasma 4 concentration 2 2 4 6 8 Time in hours FIG. 4 Log drug concentration vs. time. For drugs whose t$ does not vary with plasma concentration, to increase the duration of a given effect by 1 half-life it is necessary to increase the peak plasma concentration by a factor of 2.

V. bolus injection. For explanation see text. is in communication with a peripheral compartment (volume V 2 ) and the flux between the compartments is determined by the rate constants k 1 2 and k 2 i and the concentration difference between them. Elimination occurs only from the central compartment and is irreversible, the rate being determined by the elimination rate constant ke. T h e compartments in the model are of course mathematical and not anatomical entities. T h e biological explanation of the biphasic nature of Fig.

Phenacetin, phenytoin and guanoxan, and it is possible that genetic polymorphism for debrisoquine metabolism may represent a polymorphism for a n u m b e r of other drugs. 2. Genetic polymorphism affecting phase 2 reactions Acetylator types T h e rate limiting step in the elimination of the antituberculous drug isoniazid is acetylation, which occurs in the liver. T h e frequency distribution of isoniazid half-lives shows a bimodal pattern, the mean plasma half-life of subjects who rapidly acetylate isoniazid being one-third that of the mean value for slow acetylators.

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