Physiological pharmacokinetics and membrane transport for drug delivery research

In the case of patients undergoing dentistry and oral surgery, several drugs, including anaesthetics, antibiotics, analgesics, muscle relaxants, steroids, antidepressants and anticancer drugs are administered. Physiological pharmacokinetics is the best way to integrate the processes of drug absorption, distribution, metabolism and excretion (ADME). We have developed physiological pharmacokinetic models for β-lactam antibiotics, quinolone antibiotics, a muscle relaxant and anticancer drugs. These models enable us to compare the characteristics of drug ADME among different derivatives and to predict drug concentrations in target organs. As far as the factors affecting drug ADME are concerned, plasma membrane transport is one of the most important. The molecular mechanism of drug transport is very important as far as the bioavailability and targeting efficiency are concerned. Members of the ATP binding cassette (ABC) transporter superfamily, such as ABCB1, ABCC4 and ABCG2 have been shown to play an important role in drug efflux as a part of detoxifying system in the body. The expression and function of the transporters is not static, but can be up- or downregulated by several factors including oxidative stress, osmotic pressure and substrates of the transporter as well as by cell-to-cell interactions. Thus, plasma membrane transporters can act as a part of the dynamic interface in the body. For safe, efficient and rational drug development and treatment, it is important to understand the physiological role of these transporters.