2006
DOI: 10.1590/s0103-84782006000100056
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Multi-drug resistance (MDR1) gene and P-glycoprotein influence on pharmacokinetic and pharmacodymanic of therapeutic drugs

Abstract: (MDR1) gene expressed in tumor cells and also in several normal tissues, such as intestine, liver, kidney, blood-brain barrier, spinal cord, and placenta. P-gp has been identified in mice, rat, bovine, monkey, rodents, and human beings and has been receiving a particular clinical relevance because this protein expression limits brain access and intestinal absorption of many drugs. This protein plays a role as a protective barrier against a wide variety of substrates, avoiding drug entry into the central nervou… Show more

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Cited by 36 publications
(21 citation statements)
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References 37 publications
(78 reference statements)
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“…Also cytochrome P450 3A (CYP3A), a major CYP enzyme, is highly expressed and accounts for metabolism of approximately 50% of therapeutic drugs (Martignoni et al, 2006). The influence of P-gp and CYP3A on the pharmacokinetics and pharmacodynamics of drugs has been widely studied; drug-drug interactions (DDIs) based on their activities are responsible for many unexpected/altered therapeutic effects (Guengerich, 2001;Linardi and Natalini, 2006).…”
Section: Introductionmentioning
confidence: 99%
“…Also cytochrome P450 3A (CYP3A), a major CYP enzyme, is highly expressed and accounts for metabolism of approximately 50% of therapeutic drugs (Martignoni et al, 2006). The influence of P-gp and CYP3A on the pharmacokinetics and pharmacodynamics of drugs has been widely studied; drug-drug interactions (DDIs) based on their activities are responsible for many unexpected/altered therapeutic effects (Guengerich, 2001;Linardi and Natalini, 2006).…”
Section: Introductionmentioning
confidence: 99%
“…In our analysis, we also took into account the possible role of ACE-I in the modification of P-gp expression. The data from the literature show that the mechanism of action of this drug is different and ACE-inhibitors are neither P-gp substrates nor inhibitors [12]. Also, the fact that all of the examined children received the same dose of ACE-I during the whole therapy, in contrast to the dose of CyA, which was reduced after 6 months of treatment, may confirm that it is CyA which is responsible for changing the P-gp expression.…”
Section: Discussionmentioning
confidence: 91%
“…Pgp has been identified in canines, rodents, bovine, monkey and human beings [25]. This protein has a structure that comprises a chain of approximately 1280 aminoacid residues [26], with an N-C terminal structure ( Fig.…”
Section: Mechanisms For Drug Resistancementioning
confidence: 99%
“…Pgp has also been shown to transport hormones from the adrenal gland and the uterine epithelium. Pgp binds and transports through the cell a variety of substrates which are of variable sizes and are mainly hydrophobic with many of them having aromatic rings in their structure (Table 1) [7,21,25].…”
Section: Mechanisms For Drug Resistancementioning
confidence: 99%