Pharmacokinetics Pharmacological differences

We are indebted to the authors from the first edition who have worked to update their chapters, but are sad to report that Mary Berg, author of the chapter on Pharmacological Differences between Men and Women, died on October 1, 2004. She was an esteemed colleague and effective advocate for studying sex differences in pharmacokinetics and... 

The drive to produce stereoisomerically pure drugs is based on the recognition that there are pharmacological differences between drug stereoisomers. These differences are addressed in the third section of this book, which discusses the pharmacokinetic, plasma protein binding, efficacy, toxicity, and biotransformation of stereoisomeric drugs. 

Oxaprozin (Daypro) has similar pharmacological properties, adverse effects, and therapeutic uses to those of other propionic acid derivatives. However, its pharmacokinetic properties differ considerably. Peak plasma levels are not achieved until 3 to 6 hours after an oral dose, whereas its half-life of 40 to 60 hours allows for once-daily adminisffation. 

Such factors may change not only the kinetics of an enzyme reaction but also the whole pattern of metabolism, thereby altering the bioavailability, pharmacokinetics, pharmacological activity, or toxicity of a xenobiotic. Species differences in response to xenobiotics must be considered during the extrapolation of pharmacological and toxicological data from experiments in animals to humans. The primary factors in these differences probably are the rate and pattern of drug and xenobiotic metabolism in the various species. 

In relation to the administration of medicines for animals, the pharmacological differences and local laws have to be observed. The pharmacokinetics of every active substance is different in each species. For anunals, especially cats, the toxic concentration of many human medicines is lower than the therapeutic dose in humans due to differences in metabolism of medicines. For example, in cats, the administratirm of acetaminophen (paracetamol) very quickly leads to intoxication with methemoglobin formation, anemia, hemoglobinuria and liver damage, as they may metabolise the medicine poorly. 

The separation of enantiomers is a very important topic to the pharmaceutical industry. It is well recognized that the biological activities and bioavailabilities of enantiomers often differ [1]. To further complicate matters, the pharmacokinetic profile of the racemate is often not just the sum of the profiles of the individual enantiomers. In many cases, one enantiomer has the desired pharmacological activity, whereas the other enantiomer may be responsible for undesirable side-effects. What often gets lost however is the fact that, in some cases, one enantiomer may be inert and, in many cases, both enantiomers may have therapeutic value, though not for the same disease state. It is also possible for one enantiomer to mediate the harmful effects of the other enantiomer. For instance, in the case of indacrinone, one enantiomer is a diuretic but causes uric acid retention, whereas the other enantiomer causes uric acid elimination. Thus, administration of a mixture of enantiomers, although not necessarily racemic, may have therapeutic value. 

Dtug interactions can cause serious problems in clinical practice especially when the affected dmg has the potential to be highly toxic. Furthermore, pharmacokinetic interactions are clinically important if the affected dmg has a narrow therapeutic range (i.e. small difference between the minimum effective concentration and the toxic concentration Fig. 1) and a steep concentration-response curve (i.e. significant alterations in pharmacological and/or adverse effects caused by small changes in blood concentration). 

All clinically used opiates have the same pharmacology since they all act on the mu receptor with the exception of the kappa agonist, pentazocine. Opiates are used to relieve moderate to severe pain whatever the cause (accidents, post-operative pain, cancer, etc.) and are used pre-, intra- and post-operatively. The mu opiates differ only in potency and pharmacokinetics. Examples are ... 

Available parenteral iron preparations have similar efficacy but different pharmacologic, pharmacokinetic, and safety profiles (Table 33-5). The newer products, sodium ferric gluconate and iron sucrose, appear to be better tolerated than iron dextran. 

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