Toxicant transport by P-glycoprotein

The pharmacogenetics of drug transporters is increasingly recognized as a critical factor influencing interindividual variability in drug absorption, distribution, and elimination. These membrane-bound proteins regulate drugs' movement across cellular barriers by actively pumping them out (efflux) or facilitating their uptake (influx). Among the major transporter families, ATP-binding cassette (ABC) and solute carrier (SLC) transporters play particularly prominent roles. Genetic polymorphisms...

Carrier-mediated transport is a pivotal process in drug absorption, particularly for lipid-insoluble drugs, and encompasses facilitated diffusion and active transport. Facilitated diffusion allows drugs to move along their concentration gradient without energy expenditure, while active transport utilizes ATP to drive drug movement against this gradient.
Active transport involves two types of membrane-spanning transporters: uptake and efflux. Uptake transporters are expressed in the small...

Poison can be effectively removed from the gastrointestinal (GI) tract through various decontamination procedures.
Antidotes serve a crucial role in counteracting the effects of poison by inhibiting enzymes responsible for producing harmful drug metabolites. In some cases, these toxic metabolites can be neutralized by endogenous cosubstrates, which are maintained at specific concentrations to prevent interaction with cellular macromolecules and subsequent cell death.
Renal excretion is the...

Once the process of glomerular filtration is completed, blood carrying unfiltered drug molecules traverses through efferent arterioles and makes its way into the peritubular capillaries in the proximal tubule. A variety of carriers play a pivotal role in actively secreting drugs from these peritubular capillaries into the tubular fluid. The organic anion transporter transfers acidic drugs, against an electrochemical gradient, from the peritubular capillaries into the renal tubule cells and...

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...

Drug transporters are critical in drug absorption, distribution, and excretion processes. They should be included in physiological-based pharmacokinetic (PBPK) models, which help predict human drug disposition. However, predicting this is challenging during drug development, especially when liver transport is involved. However, with a realistic representation of body transport processes, an accurate model may be possible.
A recent model describes pravastatin's hepatobiliary excretion,...