Pharmacokinetics interactions

Pharmacokinetic interaction between fluoroquinolones and other drugs 98MI5. 

Interactions resulting from a change in the amount of diug reaching the site of action are called pharmacokinetic interactions (Fig. 1). A co-administered diug can affect any of the processes of absorption, distribution, metabolism, and excretion of the original diug, which are determinants of its pharmacokinetic profile [1-3]. 

Drug Interactions. Figure 1 Increase in drug concentration caused by pharmacokinetic interactions. Shadow represents the therapeutic range. 

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). 

Medications that have been used as treatment for anxiety and depression in the postwithdrawal state include antidepressants, benzodia2epines and other anxiolytics, antipsychotics, and lithium. In general, the indications for use of these medications in alcoholic patients are similar to those for use in nonalcoholic patients with psychiatric illness. However, following careful differential diagnosis, the choice of medications should take into account the increased potential for adverse effects when the medications are prescribed to alcoholic patients. For example, adverse effects can result from pharmacodynamic interactions with medical disorders commonly present in alcoholic patients, as well as from pharmacokinetic interactions with medications prescribed to treat these disorders (Sullivan and O Connor 2004). 

Pharmacokinetic interactions between cyclosporine and protease inhibitors in HIV+ subjects. Drug Metab Pharmacokinet 18 114-120... 

In vitro studies have shown that memantine produces minimal inhibition of CYP450 enzymes CYP1A2, 2A6, 2C9,2D6, 2E1, and 3A4. These data indicate that no pharmacokinetic interactions with drugs metabolized by these enzymes should be expected.38... 

Vigilance for drug-drug interactions is required because of the greater number of medications prescribed to elderly patients and enhanced sensitivity to adverse effects. Pharmacokinetic interactions include metabolic enzyme induction or inhibition and protein binding displacement interactions (e.g., divalproex and warfarin). Pharmacodynamic interactions include additive sedation and cognitive toxicity, which increases risk of falls and other impairments. 

As the number of medications that a patient takes increases, so does the potential for DDIs. Disease severity, patient age, and organ dysfunction are all risk factors for increased DDIs. In general, DDIs can be broken down into two categories (1) pharmacokinetic interactions and (2) pharmacodynamic interactions. 

Most pharmacokinetic interactions in transplantation occur due to interactions with the CYP enzyme system however, several interactions have been shown to occur via alternative mechanisms. One of the most notable is that seen between tacrolimus and some of the prokinetic agents. Cisapride and metoclopramide have been shown to increase the absorption of tacrolimus by enhancing gastric emptying.41... 

In addition to the numerous pharmacokinetic interactions seen with the maintenance immunosuppressants, there also exists the possibility for pharmacodynamic interactions. An in-depth review of pharmacodynamic interactions with maintenance immunosuppressive agents goes beyond the scope of this chapter. 

Paclitaxel also may be given concurrently with doxorubicin or epirubicin as a combination regimen. Pharmacokinetic interactions make these regimens more difficult to give. 

A. Johne, J. Brockmoller, S. Bauer, A. Maurer, M. Langheinrich, and I. Root, Pharmacokinetic interaction of digoxin with an herbal extract from St. John s wort (Hypericum perforatum). Clin. Pharmacol. Ther., 66, 338-345 (1999). 

Finally, a pharmacokinetic interaction between betablocker therapy and ACEID genotype has been observed in patients with congestive heart failure. Almost 90% of patients were treated with an ACE inhibitor. In the entire cohort of 328 patients transplant-free survival was significantly poorer in patients with a D allele. This adverse outcome was prevented by concomitant treatment with betablocker and enhanced in patients without betablockers [38]. 

Ioannides, C., Pharmacokinetic interactions between herbal remedies and medicinal drugs, Xenobiotica, 32, 451, 2002. 

Bertz, R.J. and Granneman, G.R. (1997) Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clinical Pharmacokinetics, 32 (3), 210-258. 

Legathe A, Hoener B-A, Tozer TN. 1994. Pharmacokinetic interaction between benzene metabolites, phenol and hydroquinone, in B6C3F1 mice. Toxicol Appl Pharmacol 124 131-138. 

Pharmacokinetic interactions Preliminary evidence suggests that Saint-John s-wort induces the cytochrome oxidase enzyme isoform CYP3A4 (Ernst 1999). This raises the potential for pharmacokinetic interactions with drugs metabolized by the same enzyme. A few cases have been reported of reduced warfarin levels (Yue et al. 2000). Similar interactions have also been reported for concurrent use with digoxin, theophylline, and cyclosporin (Nebel et al. 1999 Ruschitzka et al. 2000 Johne et al. 1999). As with any other medication, potential interactions should be considered when taking a combination of drugs. 

Pharmacokinetic Interactions. Remember that pharmacokinetics is the study of what the body does to the medication. This includes how the body transports, inactivates (i.e., metabolizes), and eliminates the medication. Sometimes, one medication can change the way the body handles another medication. This is known as a pharmacokinetic interaction. There are two types of pharmacokinetic interactions. One type occurs in the medication transportation system, and the other occurs in the medication elimination system. 

The decision to use a psychotropic drug must take into account the potential risks and benefits. This should be discussed with the patient and/ or carer. Before prescribing, a full evaluation of the symptoms should be made and the diagnosis confirmed. Polypharmacy should be avoided. If a drug combination is necessary, the pharmacod)mamic and pharmacokinetic interactions should be considered. 

Albro PW, Corbett JT, Schroeder JL, Jordan S, Matthews HB (1982) Pharmacokinetics, interactions with macromolecules and species differences in metabolism of DEHP. Environ Health Perspect 45 19-25... 

Whenever possible, interaction studies should not only be pharmacokinetic but should also include pharmacodynamic measurements in order to assess the likely clinical effect of an observed pharmacokinetic interaction. Furthermore, if possible, the design should go some way in explaining the mechanism of interaction. For example, measurement of a metabohte in plasma or urine may help to distinguish changes in elimination from changes in absorption as the reason for the change in AUC of the parent drug. 

It is not necessary to monitor gabapentin plasma concentrations to optimize therapy. Further, because there are no significant pharmacokinetic interactions with other commonly used anti-epileptic drugs, the addition of gabapentin does not alter the plasma levels of these drugs appreciably. 

Oxycodone/Lorazepam/Ethanol Multiple oral doses of pregabalin were coadministered with oxycodone, lorazepam, or ethanol. Although no pharmacokinetic interactions were seen, additive effects on cognitive and gross motor functioning were seen when pregabalin was coadministered with those drugs. 

Dose adjustment for combination therapy with saquinavir For serious toxicities that may be associated with saquinavir mesylate, the drug should be interrupted. Saquinavir mesylate at doses less than 1,000 mg with ritonavir 100 mg twice daily are not recommended since lower doses have not shown antiviral activity. For recipients of combination therapy with saquinavir mesylate and ritonavir, dose adjustments may be necessary. These adjustments should be based on the known toxicity profile of the individual agent and the pharmacokinetic interaction between saquinavir and the coadministered drug. Health care providers should refer the complete monographs for these drugs for comprehensive dose adjustment recommendations and drug-associated adverse reactions of nucleoside analogues. 

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