Andersen M E
Neurobehav Toxicol Teratol. 1981 Winter;3(4):383-9.
Physiological and biochemical factors determine the kinetic patterns of uptake, distribution, metabolism, and elimination of inhaled gases and vapors. For metabolically inert gases, true equilibrium is achieved after appropriately long exposures and the overall shape of the time-course curves of uptake and elimination should be concentration-independent. At equilibrium, achieved internal concentrations will be linearly related to exposure concentration. The rate of approach to equilibrium depends on blood flows for poorly soluble chemicals and on alveolar ventilation for soluble gases and vapors. For metabolized gases and vapors, steady-state is achieved where net pulmonary uptake replaces chemical removed from the circulation by metabolism. The shape of time-course curves for soluble, well-metabolized chemicals will be concentration-dependent, and steady-state blood:gas concentration ratios will be complexly related to inhaled concentrations. Physiological models of inhalation pharmacokinetics allow extrapolation of results in one species to untested species, based on knowledge of changing physiology between animal-to-animal. Two potential applications of interspecies extrapolation are discussed.
生理和生化因素决定了吸入气体和蒸气的摄取、分布、代谢及消除的动力学模式。对于代谢惰性气体，经过适当长时间的暴露后可达到真正的平衡，摄取和消除的时程曲线的总体形状应与浓度无关。在平衡状态下，体内达到的浓度将与暴露浓度呈线性关系。达到平衡的速率取决于难溶性化学物质的血流以及可溶性气体和蒸气的肺泡通气。对于代谢性气体和蒸气，当肺的净摄取量取代因代谢从循环中清除的化学物质时，达到稳态。可溶性、代谢良好的化学物质的时程曲线形状将取决于浓度，稳态血-气浓度比将与吸入浓度复杂相关。吸入药代动力学的生理模型允许基于对不同动物间生理变化的了解，将一个物种的结果外推至未测试的物种。文中讨论了种间外推的两种潜在应用。
