Pharmacokinetic-pharmacodynamic drug interactions

Davis MP, Walsh D Methadone for relief of cancer pain A review of pharmacokinetics, pharmacodynamics, drug interactions and protocols of administration. Support Care Cancer 2001 9 73. [PMID 11305074]... 

Williams D, Feely J. Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clin Pharmacokinet 2002 41(5) 343-70. 

J.R.B.J. Brouwers, and P.A.G.M. de Smet, Pharmacokinetic-pharmacodynamic drug interactions with nonsteroidal anti-inflammatory drugs. Clin. Pharmacokinet. 27 462-485, 1994. 

Keywords Pharmacokinetics Pharmacodynamics Drug-drug interactions Adverse drug reactions... 

Ragueneau I, Poirier JM, Radembino N, Sao AB, Funck-Brentano C, Jaillon P. Pharmacokinetic and pharmacodynamic drug interactions between digoxin and macrogol 4000, a laxative polymer, in healthy volunteers. Br J Clin Pharmacol 1999 48(3) 453-6. 

Pharmacokinetic drug interactions occur where one drug affects the absorption, distribution, metabolism or excretion of the other. Pharmacokinetic drug interactions are harder to predict than pharmacodynamic drug interactions and in many cases, affect different patients differently. 

Vourvahis, M. and Kashuba, A. D. (2007) Mechanisms of pharmacokinetic and pharmacodynamic drug interactions associated with ritonavir-enhanced tipranavir. Pharmacotherapy 27, 888-909. 

Give several examples of warfarin s role in pharmacokinetic and pharmacodynamic drug interactions. 

Mason BJ, Goodman AM, Dixon RM, Hameed MHA, Hulot T, Wesnes K, Hunter JA, Boye-son MG. A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. Neuropsychopharmacology. (2002) 27, 596-606. 

Drug-drug interactions Pharmacokinetic and/or pharmacodynamic interactions Pharmacokinetic and/or pharmacodynamic consequence of multiple drug therapy... 

The major drug interactions of antidepressants are shown in Table 35—6.9,19,30 Antidepressants cause both pharmacodynamic (e.g., additive pharmacologic effects) and pharmacokinetic (e.g., changes in drug levels) interactions with other medications. 

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. 

Drug-specific considerations in antimicrobial selection include the spectrum of activity, effects on nontargeted microbial flora, appropriate dose, pharmacokinetic and pharmacodynamic properties, adverse-effect and drug-interaction profile, and cost. 

Pharmacokinetic properties Pharmacodynamic properties Adverse-effect potential Drug-interaction potential Cost... 

Herbette, L. G., Pharmacokinetic and pharmacodynamic design of lipophilic drugs based on a structural model for drug interactions with biological membranes, Pest. Sci. 35, 363-368 (1992). 

Yuan R, Flockhart DA, Balian JD Pharmacokinetic and pharmacodynamic consequences of metabolism-based drug interactions with alprazolam, midazolam, and triazolam. J Clin Pharmacol 1999,39 1109-1125. 

Therapeutic failure may be the result of nonadherence to medication, development of drug resistance, intolerance to one or more medications, adverse drug-drug interactions, or pharmacokinetic-pharmacodynamic variability. 

Drug interactions with the BZs are generally pharmacodynamic or pharmacokinetic (Table 68-11). The combination of BZs with alcohol or other CNS depressants may be fatal. 

Human pharmacology (Phase I) Assess tolerance Define/describe pharmacokinetics and pharmacodynamics Explore drug metabolism and drug interactions Estimate activity Dose-tolerance studies Single and multiple dose PK and/or PD studies Drug interaction studies... 

Apart from patient-specific parameters, external factors - most importantly the concomitant uptake of certain other chemicals present in diet, environment and especially other drugs - influence drug actions. Possible effects are manifold and can affect all stages of pharmacokinetic and pharmacodynamic processes in the body. Also direct interaction and inactivation of concomitantly administered substances are possible. Drug-drug interactions via modulation of metabolism present a very hot topic in pharmaceutical research and drug design. 

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