Effect of heat on ACNU pharmacokinetics in normal monkey

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The effect of heat on ACNU pharmacokinetics was studied in vitro and in vivo. 1) ACNU at 10 mM was incubated with phosphate buffer (pH 7.4, shaded) at 30-42°C for 40-120 mins. Physicochemical half -life was strongly affected by the temperature, showing 88 mins for 30°C, 28 mins for 37°C, 18 mins for 40°C, and 16 mins for 42°C, respectively. 2) Blood ACNU level was sequentially measured in normal monkeys and was analysed by one compartment open model. Biological half-life was revealed 37.8±4.9mins (n=6) at 36.9±0.5°C and Vd/kg was 1.00±0.50 litter/kg. 3) The regional cerebral blood flow (rCBF) was measured before and after local brain heating under generalized hypothermia (esophageal temperature : 30.2±0.4°C, n=5). rCBF increased by heating from 20.33+6.37 ml/100g brain/ml (tissue temperature : 30.0±0.1°C) to 40.84±12.37ml/100g brain/min (37.4±0.9°C). 4) Biological half-life at the above hypothermia was 82.5±3.0 mins and Vd/kg was 1.07±0.12 litter/kg. 5) Those results indicated that half-life of ANCU depended markedly upon the blood temperature. The drug delivery to the local brain may be enhanced by heat via increased rCBF.
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