Linked Life Data

1975136

Source:http://linkedlifedata.com/resource/pubmed/id/1975136

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1990-9-27
pubmed:abstractText
Agents capable of reversing multidrug resistance (mdr) in falciparum malaria were investigated for potentiation of chloroquine accumulation and toxicity in a cell culture system. Verapamil, its analog RO11-2933, and desipramine caused a dose-dependent increase in the accumulation of chloroquine (CQ) within human and mouse hepatocytes but not human lung cells. Only those cells in which drug accumulation was enhanced by reversing agents reacted positively for P-glycoprotein (PgP)--the putative mediator of the enhanced drug efflux characteristic of mdr. Clinically achievable concentrations of verapamil (0.4 microM) and desipramine (1 microM) increased CQ accumulation within primary mouse hepatocytes by more than 50%. A well-differentiated normal human cell line (Hep-G2) was killed in media containing a combination of supraphysiological concentrations of CQ and verapamil but survived the same concentrations of either drug alone. Reversing agents may block PgP-mediated drug export from normal tissues as well as from MDR cells. Iatrogenic toxicity resulting from this accumulation of potentially toxic drugs such as CQ within normal cells could complicate the reversal of mdr in vivo.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0035-9203
pubmed:author
pubmed:issnType
Print
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
187-90
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:articleTitle
Reversal of drug-resistant falciparum malaria by calcium antagonists: potential for host cell toxicity.
pubmed:affiliation
Department of Hematology, Walter Reed Army Institute of Research, Washington, DC.
pubmed:publicationType
Journal Article