Pharmaceutical and pharmacological approaches for bioavailability enhancement of etoposide.
Etoposide, a semi-synthetic derivative of podophyllotoxin, is one of the most active and useful antineoplastic agent used routinely in firstline combination chemotherapy of testicular cancer, small-cell lung cancer and non-Hodgkin's lymphoma. Etoposide displays narrow therapeutic index, erratic pharmacokinetics and dose individualization that needs to be achieved for overcoming inter- and intra-patient variability (25-80 percent), so as to maintain proper drug exposure within a therapeutic range. Etoposide possess high plasma protein binding (97 percent) and is degraded via complex metabolic pathways. The main pharmacokinetic determinants of etoposide are still not completely defined in order to optimize the pharmaco-therapeutic parameters including dose, therapeutic schedule and route of administration. Much research has been done to determine drug-drug and herb-drug interactions for improving the bioavailability of etoposide. The present article gives insight on pharmaceutical and pharmacological attempts made from time to time to overcome the erratic inter- and intra-patient variability for improving the bioavailability of etoposide.
PK/PD-Toxicology Division, CSIR - Indian Institute of Integrative Medicine, Canal Road, Jammu 180 001, India.
Ishtiyaq Ahmad
IA
Najar
Rakesh Kamal
RK
Johri
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D001682:Biological Availability; D001798:Blood Proteins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008081:Liposomes / Q000378:metabolism; D015394:Molecular Structure; D011485:Protein Binding
D000972:Antineoplastic Agents, Phytogenic; D001798:Blood Proteins; D008081:Liposomes; D005047:Etoposide