Pharmacokinetic interactions excretion alterations

The varied and complex mechanisms involved can be broadly classified as pharmacokinetic interactions or pharmacodynamic interactions. In pharmacokinetic interactions, drugs interfere with and may alter the absorption, distribution, biotransformation, or excretion of other drugs. In pharmacodynamic interactions, which have been discussed in Chapter 2, drugs modify the intended and expected actions of other drugs. Before elaborating on the pharmacokinetic interactions, some terms will be defined. 

Pharmacokinetic interactions are adverse effects that occur due to altered body burden of a drug as a result of a coadministered drug that can occur because of the ability of one drug to alter the absorption, distribution, metabolism, and excretion (ADME properties) of the coadministered drug. Of the ADME properties, drug metabolism represents the most important and prevalent mechanism for pharmacokinetic interactions. 

Compared with pharmacodynamic interactions, pharmacokinetic drug interactions are harder to predict and will have an increased variability between patients. In pharmacokinetic interactions, one of the drugs alters the absorption, distribution, metabolism or excretion of the other. This results in an increase or decrease in the amount of drug available to have a pharmacological effect. 

One of the factors that can alter the response to drugs is the concurrent administration of other drugs. There are several mechanisms by which drugs may interact, but most can be categorized as pharmacokinetic (absorption, distribution, metabolism, excretion), pharmacodynamic (additive or antagonistic effects), or combined interactions. The general principles of pharmacokinetics are discussed in Chapters 3 and 4 the general principles of pharmacodynamics in Chapter... 

It has been estimated that 6.9% of ADRs are due to drug-drug interactions (6). The most likely reason for an adverse drug interaction is the pharmacokinetic changes that result in altered metabolism or excretion of drugs, or the... 

In a double-blind study, 13 patients with normal renal function were given a single 600-mg dose of lithium either with or without gabapentin at steady state. Gabapentin did not significantly alter the pharmacokinetics of the lithium, and no increase in adverse effects was noted. More longterm studies will be needed to confirm this lack of interaction, especially in patients with impaired renal function as both drugs are eliminated by renal excretion. ... 

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