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Thread: The Clinical Pharmacokinetic Analytic Process

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    PharmD Year 1 TomHsiung's Avatar
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    Default The Clinical Pharmacokinetic Analytic Process

    First, the importance of two-compartment modeling

    Where the end-organ for clinical response located. For the condition that end-organ are located in the Vi compartment, if the loading dose is calculated by the total volume of distribution (Vi + Vt), during the distribution phase, the drug concentration in the Vi would be much higher than that predicted by one-compartment model because the most of the administered drug amount still stays in the Vi compartment and has not adequately distributed into the Vt compartment yet.

    There are two methods to circumvent this issue. 1) Administering the loading dose at a rate slow enough to allow for drug distribution into Vt. 2) Administering the loading dose in sufficient small individual bolus doses such that the C in Vi does not exceed some predetermined critical concentration.

    On the other hand, rapid achievement of a therapeutic response would followed quickly by a loss of the therapeutic response because drug first turns up in the Vi compartment would be distributed into a larger volume of distribution rather than be eliminated from the body.

    When the drug's target organ is in the second or Vt compartment, the high C, which may be observed before distribution occurs, is not dangerous. However, plasma concentrations that are obtained before distribution is complete will not reflect the tissue concentration at equilibrium. Therefore, these plasma samples cannot be used to predict the therapeutic or toxic potential of these drugs. As a general rule, sampling of drug concentrations during the absorption/distribution phase should be avoided as these concentrations are changing very rapidly and are difficult to interpret.

    • The alpha phase for most drugs represents distribution of drug from Vi into Vt, and relatively little drug is eliminated during the distribution phase. Drugs that behave in this way are generally referred to as "nonsignificant" two-compartmental drugs. "Nonsignificant" means that if the patient is not harmed by the initially elevated drug concentration in the alpha phase and no drug samples are taken in the alpha phase, then the drug can be successfully modeled as a one-compartment drug.
    • Drugs with "significant" two-compartment modeling are those that are eliminated to a significant extent during the initial alpha phase. For these drugs, the alpha phase cannot be thought of simply as distribution because significant elimination occurs as well. When a one-compartment model is used for drugs that exhibit significant drug elimination in the alpha phase, the actual trough concentrations will be lower than those predicted by the one-compartment model.


    The factor affecting volume of distribution
    Last edited by TomHsiung; Wed 29th March '17 at 10:33pm.
    B.S. Pharm, West China School of Pharmacy, Class of 2007, Health System Pharmacist, RPh. Hematology, Infectious Disease.

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