Title: Adequate tumour quinidine levels for multidrug resistance modulation can be achieved in vivo
Abstract: The multidrug resistance (MDR) phenotype can be reversed in vitro by a number of agents thought to interact with P-glycoprotein (P-gp). Although plasma levels, adequate for MDR modulation, can be achieved with certain modulators, concern has been expressed that tumour levels may be inadequate due to high plasma protein binding. Mice bearing an MDR-positive human tumour xenograft were injected intraperitoneally with quinidine (150 mg/kg). After 2 h the mean plasma quinidine level was 1.9 μg/ml (5.1 μmol/l) and the mean tumour quinidine level was 6 μg/g. Thus tumour levels were higher than plasma levels and were within the range known to be effective in vitro. Three tumour biopsy specimens were obtained from patients who had received oral quinidine prior to surgery. Plasma and tumour levels were similar and were comparable with those measured in mice. This study should dispel fears of inadequate tumour levels of this and other modulators due to high plasma protein binding and encourage future clinical trials of modulators in MDR-positive human tumours.
Publication Year: 1992
Publication Date: 1992-01-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
Access and Citation
Cited By Count: 29
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