Pore transport and ion-pair formation are critical mechanisms for the absorption and distribution of drugs in the body.
Pore transport, also known as convective transport, is a process where small molecules like urea, water, and sugars rapidly cross cell membranes as though there were channels or pores in the membrane. Although direct microscopic evidence is limited but the concept of pores or channels is widely accepted based on physiological evidence. Despite the lack of direct microscopic evidence of such pores, this model explains renal drug excretion and hepatic drug uptake. Transport proteins may form an open channel across the cell's lipid membrane, facilitating faster diffusion of small molecules, including drugs, compared to other parts of the membrane.
On the other hand, ion-pair formation involves the binding of oppositely charged ions to form a neutral complex. The strong electrolyte drugs maintain their charge at all physiological pH values and penetrate membranes poorly. However, when paired with an oppositely charged ion, a neutral ion pair forms, which diffuses more easily across the membrane. Examples include propranolol, which forms an ion pair with oleic acid, and quinine, which pairs with hexyl salicylate.
The use of ion pairs has intriguing applications, such as the complexation of amphotericin B and DSPG in certain amphotericin B/liposomal products. Here, ion pairing can transiently alter distribution, reduce high plasma-free drug concentration, and decrease renal toxicity.
From Chapter 3:
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