0000000000560613
AUTHOR
Finn Bengtsson
Blood-brain barrier penetration of the enantiomers of venlafaxine and its metabolites in mice lacking P-glycoprotein
According to in vitro studies the enantiomers of venlafaxine display different degrees of serotonin and noradrenaline reuptake inhibition. Therefore, clarification of the enantiomeric drug distribution between serum and brain is highly warranted. To elucidate if P-glycoprotein (P-gp) in a stereoselective manner transports venlafaxine and its metabolites out of the brain we used abcb1ab double-knockout mice that do not express P-gp. A single dose of racemic venlafaxine (10 mg/kg bw) was intraperitoneally injected to knockout (-/-) and wildtype (+/+) mice. Serum and brain samples were collected 1, 3, 6 and 9 h following drug administration for analysis by LC/MS/MS. One to six hours post-dose,…
Problem solving in psychopharmacotherapy using pharmacokinetic and pharmacogenetic tests
Many problems such as non-response, pharmacokinetic interactions with clinical consequences and adverse effects (pharmacovigilance) may be observed in patients submitted to psychopharmacotherapy. These risks are increased in patients belonging to the category of “special populations”: elderly patients, children and adolescents, patients with a genetic particularity of metabolism or suffering from somatic or psychic comorbidities. Pharmacokinetic and pharmacogenetic tests are useful to solve problems in psychopharmacotherapy and thus improve efficacy and safety. Therapeutic drug monitoring (TDM) is particularly recommended in situations presented above and in patients who are non-compliant. …
Altered brain concentrations of citalopram and escitalopram in P-glycoprotein deficient mice after acute and chronic treatment
Background: According to both in vitro and in vivo data P-glycoprotein (P-gp) may restrict the uptake of several antidepressants into the brain, thus contributing to the poor success rate of current antidepressant therapies. The therapeutic activity of citalopram resides in the Senantiomer, whereas the R-enantiomer is practically devoid of serotonin reuptake potency. To date, no in vivo data are available that address whether the enantiomers of citalopram and its metabolites are substrates of P-gp. Methods: P-gp knockout (abcb1ab (-/-)) and wild-type (abcb1ab (+/+)) mice underwent acute (single-dose) and chronic (two daily doses for 10 days) treatment with citalopram (10 mg/kg) or escitalop…