Clinically relevant drug-drug interactions between antiretrovirals and antifungals.

Introduction: Complete delineation of the HIV-1 life cycle has resulted in the development of several antiretroviral drugs. Twenty-five therapeutic agents belonging to five different classes are currently available for the treatment of HIV-1 infections. Advent of triple combination antiretroviral therapy has significantly lowered the mortality rate in HIV patients.

Efflux transporters- and cytochrome P-450-mediated interactions between drugs of abuse and antiretrovirals.

Multidrug regimens and corresponding drug interactions cause many adverse reactions and treatment failures. Drug efflux transporters: P-gp, MRP, BCRP in conjunction with metabolizing enzymes (CYPs) are major factors in such interactions. Most effective combination antiretrovirals (ARV) therapy includes a PI or a NNRTI or two NRTI.

Identification and functional characterization of breast cancer resistance protein in human bronchial epithelial cells (Calu-3).

Breast cancer resistance protein (BCRP), a 72 kDa protein belongs to the subfamily G of the human ATP-binding cassette transporter superfamily. Overexpression of BCRP was found to play a major role in the development of resistance against various chemotherapeutic agents. BCRP plays an important role in absorption, distribution and elimination of several therapeutic agents.

Vitreal pharmacokinetics of biotinylated ganciclovir: role of sodium-dependent multivitamin transporter expressed on retina.

Purpose: The objective of this study was to investigate the role of sodium-dependent multiple vitamin transporter (SMVT) on Biotin-Ganciclovir (biotin-GCV) uptake on both human retinal pigmented epithelium cell line (ARPE-19) and rabbit retina. Study also aims to delineate the vitreal pharmacokinetics of biotin-GCV.

Method: ARPE-19 was employed to study the in vitro uptake experiments.

Folic acid transport via high affinity carrier-mediated system in human retinoblastoma cells.

The primary objective of this study was to investigate the expression of a specialized carrier-mediated system for folic acid and to delineate its uptake mechanism and intracellular trafficking in a human derived retinoblastoma cell line (Y-79). Uptake of [3H]Folic acid was determined at various concentrations, pH, temperatures, in the absence of sodium and chloride ions and in the presence of structural analogs, methyltetrahydro folate (MTF) and methotrexate (MTX), vitamins, membrane transport and metabolic inhibitors to delineate the mechanism of uptake. Kinetics of uptake was studied in the presence of various intracellular regulatory pathways; protein kinases A and C (PKA and PKC), protein tyrosine kinase (PTK) and calcium-calmodulin modulators.

Biotin uptake by rabbit corneal epithelial cells: role of sodium-dependent multivitamin transporter (SMVT).

Purpose: The objective of this research was to investigate the presence of sodium-dependent multivitamin transporter (SMVT) on rabbit corneal epithelial cells.

Methods: Primary cultured rabbit corneal epithelial cells (rPCECs)and freshly excised rabbit corneas were used for characterization of biotin uptake and transport, respectively. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to confirm the molecular identity of SMVT.