吸入的甲基肼在家兔体内的毒代动力学

家兔吸入111±4和162±12mg/m~3及恒速静脉输注2.1±0.1和4.1±0.1 mg·kg~(-1)·h~(-1)甲基肼(MMH),均以一室模型在体内配置,iv MMH呈二室模型。MMH经呼吸道的吸收,与恒速静脉输注一样,为表观零级速度过程。经呼吸道的滞留率高、稳定,不受吸入气中MMH浓度和动物通气量变化的影响。MMH在家兔体内分布快,呈周身分布,周室稍富集。消除较快,物质蓄积性弱;消除速度与染毒水平有一定的依赖关系,有消除饱和的趋势。肾清除只占机体总清除的50％左右,提示存在肾外消除途径。此外,对估算MMH吸入染毒的表观零级吸收速度常数k_0和实际吸收剂量Da的简化方法进行了探讨。

Toxicokinetics of inhaled monomethylhydrazine in rabbits

The toxicokinetics of inhaled mono methylhydrazine (MMH), a kind of liquid rocket propellant, was studied in rabbits and compared with that of intravenous injection (iv) and infusion. The inhaled MMH vapour concentrations were 110.9 and 161.9 mg/m3 respectively. The toxicant concentration-time curves after iv MMH in rabbits could fit two-compartments open model, but both the kinetics of inhaled and infused MMH could be described as one-compartment open model.The absorption of MMH through lungs could be characterized as an apparent zero-order process similar to that of the infused MMH. The absorption rate, which was independent of the concentration of MMHin air and the ventilation volume, was constant and hight as 98%. MMH was distributed rapidly and widely, the accumulation of it was low. The elimination of MMH in rabbits was rapid with t,1/2 = 2.37-4.44 h and was related to the level of MMH poisoning. Renal clearance was only 36.1-52.0% of the total body clearance, indicating that there were other pathways than renal elimination in rabbits. Besides, the simplified methods that could calculate the apparent zero-order absorption rate constant (k0) of inhaled MMH vapour were explored.