Influence of different doses of methyl ethyl ketone on 2,5-hexanedione concentrations in the sciatic nerve, serum, and urine of rats.

Rats were injected subcutaneously with 2,5-hexanedione (2,5-HD 2.6 m mol/kg) alone (HD group) or with 2,5-HD and methyl ethyl ketone (MEK) (2.6 m mol/kg of each agent, HD&MEK group) or with 2,5-HD 2.6 m mol/kg and 5 times that dose (13.0 m mol/kg) of MEK (HD&5MEK group). The concentration of 2,5-HD in serum and in the sciatic nerve was determined 0.5, 1, 2, 4, 8, and 16 h after administration. Urinary 2,5-HD concentration was determined from the beginning of administration up to 16 h afterward. 1) The concentration of 2,5-HD in the serum, the sciatic nerve, and the urine was increased significantly (p < 0.05) in the co-administered groups; the higher the MEK doses were, the greater was the increase. 2) The clearance of 2,5-HD from both the serum and the sciatic nerve was delayed in the co-administered groups. The highest concentration in serum and the sciatic nerve appeared at 1 and 2 h respectively. After administration, the biological halflife (t1/2) of 2,5-HD from 1 to 8 h in serum was 6.5, 5.8 and 12.0 h for the HD, HD&MEK, and HD&5 MEK groups respectively. From 8 to 16 h, the t1/2 in serum was 1.2, 3.2 and 16.6 h for the HD, HD&MEK, and HD&5MEK groups, respectively. In nerve tissue, the prolongation of clearance in the co-administered groups was greater than that in serum, the t1/2 from 2 to 8 h being 5.2, 9.6 and 19.9 h for the HD, HD&MEK, and HD&5MEK groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)