Studies on the increasing number of transporters found in the placental barrier are gaining momentum, because of their tissue-specific expression, significance in physiology and disease, and the possible utilization of the emerging knowledge in pharmacology. In the placenta, both syncytiotrophoblast and fetal capillary endothelium express transporters. Fetal exposure is determined by the net ef...

Local biotransformation enzymes and transporter proteins in tissues may exert a profound effect on drug pharmacokinetics in those tissues. Thus, the use of drugs for the treatment of benign prostatic hyperplasia (BPH) and cancer of the prostrate may be influenced by high level expression of cytochrome P450 (CYP) phase I and phase II conjugation enzymes and drug transporters. Phase I drugmetabol...

In the combination antiretroviral therapy (cART) era, prevalence of HIV-associated neurocognitive disorders (HAND) remains high, 36.2-44.8%, contributing to morbidity and mortality. Suboptimal control of HIV in the central nervous system (CNS) likely plays a role in this phenomenon, as supported by elevated neopterin and detectable HIV-1 RNA in cerebrospinal fluid (CSF) of patients on long-term...

Drug efflux pumps play a key role in drug resistance and also serve other functions in bacteria. There has been a growing list of multidrug and drug-specific efflux pumps characterized from bacteria of human, animal, plant and environmental origins. These pumps are mostly encoded on the chromosome, although they can also be plasmid-encoded. A previous article in this journal provided a comprehe...

Understanding the dynamics of drug metabolizing enzymes and transporters (METs) is critical to successful drug development. MET behavior can significantly impact drug safety. Many factors regulate enzymes and transporters, which in turn affect the pharmacokinetic properties of drugs and mediate drug interactions. Evaluation of drug interaction profiles required detailed in vitro and in vivo stu...

Tenofovir disoproxil fumarate, the prodrug of nucleotide reverse transcriptase inhibitor tenofovir, shows high efficacy and relatively low toxicity in HIV patients. However, long-term kidney toxicity is now acknowledged as a modest but significant risk for tenofovir-containing regimens, and continuous use of tenofovir in HIV therapy is currently under question by practitioners and researchers. ...

Tamoxifen is the first line drug used in the treatment of estrogen receptor-positive (ER+) breast cancer. The development of multidrug resistance (MDR) to tamoxifen remains a major challenge in the treatment of cancer. One of the mechanisms related to MDR is decrease of drug influx via overexpression of drug efflux transporters such as P-glycoprotein (P-gp/MDR1), multidrug resistance associated...

The liver plays a crucial role in the detoxification of drugs used in the treatment of many diseases. The liver itself is the target for drugs aimed to modify its function or to treat infections and tumours affecting this organ. Both detoxification and pharmacological processes occurring in the liver require the uptake of the drug by hepatic cells and, in some cases, the elimination into bile. ...

Multidrug resistance (mdr) can be defined broadly as the ability of a cell to survive ordinarily lethal doses of more than one drug. Clearly, such resistance is a critical problem in the treatment of fungal and bacterial infections and cancer. Four general, but nonexclusive, mechanisms give rise to multidrug resistance: 1) detoxification by enzymatic modification or cleavage of drug; 2) genetic...

T kidney plays a critical role in the removal of a wide range of endogenous substances, drugs, and metabolites from the body. Understanding the role of renal clearancemechanisms as a source of intersubject variability in pharmacokinetics is also important. It is becoming increasingly evident that carrier-mediated drug-efflux transporters in the intestine, liver, and kidney contribute to drug el...