Effect of heat on ACNU pharmacokinetics in normal monkey

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.