TY - JOUR
T1 - Preclinical evidence of enhanced analgesic activity of duloxetine complexed with succinyl-β-cyclodextrin
T2 - A comparative study with cyclodextrin complexes
AU - Seggio, Mimimorena
AU - Contino, Annalinda
AU - Maccarrone, Giuseppe
AU - Parenti, Carmela
AU - Merlo, Sara
AU - Pappalardo, Giuseppe
AU - Giuffrida, Alessandro
AU - Chiechio, Santina
PY - 2019/7/20
Y1 - 2019/7/20
N2 - Chronic pain represents one of the most important public health problems, with a great prevalence of comorbidity with depression and cognitive decline. Antidepressants such as duloxetine, a serotonin-norepinephrine reuptake inhibitor, represent an essential part of the therapeutic strategy for chronic pain management in addition to classical analgesics. Duloxetine is endowed with good efficacy and a good profile of safety and tolerability. Yet, duloxetine is metabolized by the cytochrome P450 system 2D6 and 1A2 (CYP2D6 and CYP1A2) and it exhibits moderate inhibitory activity on CYP2D6, resulting in side effects and metabolic interactions that may occur on a long term therapeutic schedule. Cyclodextrins (CyDs) are used in pharmaceutical applications for numerous purposes, including the improvement of drug bioavailability. In order to evaluate their effects on the activity of duloxetine, we first spectrophotometrically studied the host–guest complexes obtained combining duloxetine and different β-CyD derivatives (β-CyD, β-CyDen-c-(Glu-Glu), and succinyl-β-CyD) and then performed in vivo and in vitro studies. Among duloxetine/CyDs complexes, succinyl-β-CyD ameliorated the analgesic activity of duloxetine in the tail flick test and in the formalin test in mice and significantly protected the drug from CYP2D6 metabolism.
AB - Chronic pain represents one of the most important public health problems, with a great prevalence of comorbidity with depression and cognitive decline. Antidepressants such as duloxetine, a serotonin-norepinephrine reuptake inhibitor, represent an essential part of the therapeutic strategy for chronic pain management in addition to classical analgesics. Duloxetine is endowed with good efficacy and a good profile of safety and tolerability. Yet, duloxetine is metabolized by the cytochrome P450 system 2D6 and 1A2 (CYP2D6 and CYP1A2) and it exhibits moderate inhibitory activity on CYP2D6, resulting in side effects and metabolic interactions that may occur on a long term therapeutic schedule. Cyclodextrins (CyDs) are used in pharmaceutical applications for numerous purposes, including the improvement of drug bioavailability. In order to evaluate their effects on the activity of duloxetine, we first spectrophotometrically studied the host–guest complexes obtained combining duloxetine and different β-CyD derivatives (β-CyD, β-CyDen-c-(Glu-Glu), and succinyl-β-CyD) and then performed in vivo and in vitro studies. Among duloxetine/CyDs complexes, succinyl-β-CyD ameliorated the analgesic activity of duloxetine in the tail flick test and in the formalin test in mice and significantly protected the drug from CYP2D6 metabolism.
KW - Cyclodextrin derivatives
KW - CYP2D6
KW - Depression
KW - Drug delivery
KW - Duloxetine
KW - Inclusion complexes
KW - Pain
UR - http://www.scopus.com/inward/record.url?scp=85066613983&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066613983&partnerID=8YFLogxK
U2 - 10.1016/j.ijpharm.2019.05.077
DO - 10.1016/j.ijpharm.2019.05.077
M3 - Article
C2 - 31158453
AN - SCOPUS:85066613983
VL - 566
SP - 391
EP - 399
JO - International Journal of Pharmaceutics
JF - International Journal of Pharmaceutics
SN - 0378-5173
ER -