A new three compartment model incorporated with dilution process

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Three compartment pharmacokinetic(PK) model is usually used to explain the uptake and disposition process of intravenously administered drug. In this model the hypothesis that instantaneous dilution would be occurred just after administering the drug into blood circulation, but we had some studies in which that hypothesis showed to be wrong and some dilution time is required to conform uniform distribution in the central compartment. This null-hypothesis might mislead correct estimation of serium concentration time profile especially in the second order transient period after bolus dosing or by large dose constant infusion. We had incorporated a dilution process model with this three compartment model(hybrid model) and had tried to estimate serium concentration in the transient period and in medium and slowly decreasing period such that distribution and elimination phase in pharmacokinetic time profile.We had swine animal study(n=9). They were anesthetized by isoflurane and propofol wa … More s administered for 5 minutes in rapid infusion rate of 2mg/kg/min. After infusion terminated swine were anesthetized until 135 minutes passed. Blood was sampled by predetermined time intervals both in infusion continued and terminated phase throughout study period. Sampled blood was separated to serium by centrifuge and analyzed by high performance liquid, chromatography. Mean pooled data were used to estimate PK constants and dilution model constants by using the least squared method. Estimation performance was compared by calculating summation of the squared difference between estimated and measured data in the range of overall periods(EP_<all>) and in the range of rapid infusion period(EP_<rpd>).EP_<all> in new hybrid model and in conventional three compartment PK model were 155.0 vs 207.7 (mcg/ml)^2 respectively and EP_<rpd> were 97.7 vs 197.8 (mcg/ml)^2 respectively in each model.In conclusion our new hybrid model can estimate more accurately concentration time profile both in rapid transition and slow distribution and elimination phase. Less