TY - JOUR
T1 - Physiological pharmacokinetics and membrane transport for drug delivery research
AU - Terasaki, Tetsuya
AU - Ohtsuki, Sumio
PY - 2005/9/1
Y1 - 2005/9/1
N2 - 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.
AB - 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.
KW - ABC transporter
KW - Drug delivery
KW - Physiological pharmacokinetics
KW - Transport
UR - http://www.scopus.com/inward/record.url?scp=33646462749&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33646462749&partnerID=8YFLogxK
U2 - 10.1016/j.ics.2005.06.070
DO - 10.1016/j.ics.2005.06.070
M3 - Article
AN - SCOPUS:33646462749
VL - 1284
SP - 266
EP - 273
JO - International Congress Series
JF - International Congress Series
SN - 0531-5131
ER -