Gonda I, Gipps E
Department of Pharmacy, University of Sydney, NSW, Australia.
Pharm Res. 1990 Jan;7(1):69-75. doi: 10.1023/a:1015891727080.
A mathematical model was developed to describe the rate processes involved in the disposition of drugs placed in their delivery systems into the human nasal cavity. The model contains first-order parallel and sequential irreversible rate processes representing the convective drug and carrier transport by fluid flow, mucociliary clearance and peristalsis, drug release and absorption, and decomposition of the drug prior to its appearance in the systemic circulation. The numerical values of the parameters used are based on literature data from clearance studies of nonabsorbable markers deposited in the human nasal cavity, and data obtained under a variety of experimental conditions are consistent with the model. The effect of bioadhesive carriers is successfully simulated by reducing the mucociliary clearance rate constants for the transport from the posterior part of the nose into the gastrointestinal tract. The simulation shows that bioadhesion improves bioavailability and reduces the variability in absorption which might be caused by a variable pattern of deposition in the nose. Variable bioavailability could result from removal of the drug from the nasal cavity by sniffing, blowing, or wiping the nose, leading to different drug residence times in the nose. The model simulations further suggest that drug decomposition in the nose, while lowering bioavailability, also reduces variable absorption due to variable residence times of the drug in the nose.
建立了一个数学模型，用于描述置于给药系统中的药物进入人体鼻腔后的处置过程中的速率过程。该模型包含一级平行和顺序不可逆速率过程，分别代表药物和载体通过流体流动、黏液纤毛清除和蠕动的对流运输、药物释放和吸收，以及药物在进入体循环之前的分解。所用参数的数值基于人体鼻腔内沉积的不可吸收标记物清除研究的文献数据，并且在各种实验条件下获得的数据与该模型一致。通过降低从鼻腔后部进入胃肠道的运输的黏液纤毛清除速率常数，成功模拟了生物黏附载体的作用。模拟结果表明，生物黏附提高了生物利用度，并降低了可能因鼻腔内沉积模式变化而导致的吸收变异性。可变的生物利用度可能是由于通过嗅、擤或擦鼻从鼻腔中清除药物，导致药物在鼻腔中的停留时间不同。模型模拟进一步表明，药物在鼻腔中的分解虽然降低了生物利用度，但也减少了由于药物在鼻腔中停留时间变化而导致的可变吸收。
