Abstract: Historically, it has been assumed that only free drug concentration is the pharmacologically active species. This article reviews the theoretical.

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This article reviews the theoretical pharmacological and pharmacokinetic justifications for monitoring free drug levels. British Journal of Clinical Pharmacology [01 Dec , 44 6: Twelve renal transplant patients were selected on the basis of the stability of their cyclosporine A blood concentrations for the previous 3 months. Some examples such as the modification of furosemide pharmacokinetics in acute renal failure, the impaired metabolism of opiate analgesics in hepatic insufficiency, the alterations of the usual disposition process in salicylic acid intoxication, and the influence of cardiac failure upon some drugs pharmacokinetics, have been chosen to illustrate some of the aspects discussed.

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Therapeutic Drug Monitoring [01 Jan , 10 2: The distribution can also be influenced by circulatory disorders modifying local blood flows and thus impeding drug entry into the tissues. The resulting modifications in the free fraction of the drug can cause a change in the volume of distribution.

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The resulting modifications in the free fraction of the drug can cause a change in the volume of distribution. The different methods which can be used for determining free drug level are presented.

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In the future, much more effort must be devoted in order to provide sufficient information on the clinical relevance of free drug concentration. Therefore, it was suggested that trimetazidine may be coadministered with cyclosporine A without cyclosporine A dosage adjustment. Before and after trimetazidine administration, cyclosporine A blood concentrations, plasma interleukin-2 and soluble interleukin-2 receptor levels were measured. Review, Journal Article Abstract Historically, it has been assumed that only free drug concentration is the pharmacologically active species.

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The different methods which can be used for determining free drug level are presented. Some simple rules for making a rational selection of drugs in pathological states are also outlined. The determinants likely to influence plasma protein binding and the free concentrations of drugs are delineated.

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Review, Journal Article Abstract This article attempts to help in the understanding of the mechanisms responsible for a modified drug pharmacokinetic profile in disease states. Twelve renal transplant patients were selected on the basis of the stability of their cyclosporine A blood concentrations for the previous 3 months.

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Their advantages and drawbacks as well as their reliability and suitability for routine clinical practice are discussed. The resulting modifications in the free fraction of the drug can cause a change in the volume of distribution. In renal allograft recipients, trimetazidine Vastarel was proposed to be associated with the classic immunosuppressant treatments because it displays anti-ischaemic effects which may protect against cyclosporine A nephrotoxicity.

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But, for all these drugs, there is a considerable lack of data establishing the correlations between therapeutic or toxic response and free concentration. Changes in absorption kinetics can be due to altered gastrointestinal peristalsis and secretions as well as modifications of splanchnic blood flow.

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4 Commentsto Barrej

  1. Moogucage says:

    Before and after trimetazidine administration, cyclosporine A blood concentrations, plasma interleukin-2 and soluble interleukin-2 receptor levels were measured. The objective of this work was to assess the possibility of coadministering cyclosporin A, Sandimmun, and trimetazidine.

  2. Tezragore says:

    The data showed that neither cyclosporin A blood pharmacokinetic parameters, Cmax, tmax, AUC, nor the concentrations of interleukin-2 and soluble interleukin-2 receptors were significantly modified. In the future, much more effort must be devoted in order to provide sufficient information on the clinical relevance of free drug concentration.

  3. Dougis says:

    Pathological states may affect the binding of drugs to plasma proteins, mainly human serum albumin and alpha 1 acid glycoprotein.

  4. Zolot says:

    Changes in absorption kinetics can be due to altered gastrointestinal peristalsis and secretions as well as modifications of splanchnic blood flow. Their advantages and drawbacks as well as their reliability and suitability for routine clinical practice are discussed.

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