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Drug Metabolism & Disposition

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Abstract

Dose dependence in the plasma pharmacokinetics and uptake kinetics of 2',3'-dideoxyinosine into brain and cerebrospinal fluid of rats.

B L Hoesterey, R E Galinsky and B D Anderson
Drug Metabolism and Disposition September 1991, 19 (5) 907-912;
B L Hoesterey
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R E Galinsky
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B D Anderson
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Abstract

Dose dependence in the plasma pharmacokinetics of 2',3'-dideoxyinosine (ddI) was examined during and after 2-hr iv infusions in rats at infusion rates of 12.4, 32.7, and 125 mg/kg/hr. After termination of the infusions, the disappearance of ddI from plasma was distinctly biphasic, suggesting that the majority of ddI is eliminated before distribution equilibrium is achieved. The mean alpha t1/2 following the infusions was 2.7 min and was independent of dose. The mean terminal half-life (beta t1/2) was approximately 24 min and also independent of dose. Nonlinear pharmacokinetic behavior in plasma after infusions was manifested in a decreased clearance with increasing dose, as determined from steady state plasma concentrations of ddI during infusions. In parallel with the decreased clearance, the apparent volume of distribution of the central compartment, Vcapp, decreased with increasing dose. Nonlinearity in clearance with increasing dose could be accounted for using a model which includes rapid, saturable tissue binding. Dose dependence in the kinetics of uptake of ddI into brain tissue and cerebrospinal fluid (CSF) was also examined during and after iv infusions. Steady state concentrations of ddI in brain tissue and CSF varied linearly with steady state plasma concentrations over a plasma concentration range of greater than 30-fold. Mean tissue to plasma concentration ratios, expressed as percentages, were 2% in CSF, 5% in brain tissue, and 1-2% in brain parenchymal tissue (corrected for the contribution of the cerebral vascular space).

 

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Drug Metabolism and Disposition
Vol. 19, Issue 5
1 Sep 1991
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Abstract

Dose dependence in the plasma pharmacokinetics and uptake kinetics of 2',3'-dideoxyinosine into brain and cerebrospinal fluid of rats.

B L Hoesterey, R E Galinsky and B D Anderson
Drug Metabolism and Disposition September 1, 1991, 19 (5) 907-912;

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Abstract

Dose dependence in the plasma pharmacokinetics and uptake kinetics of 2',3'-dideoxyinosine into brain and cerebrospinal fluid of rats.

B L Hoesterey, R E Galinsky and B D Anderson
Drug Metabolism and Disposition September 1, 1991, 19 (5) 907-912;
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