Banca de QUALIFICAÇÃO: EDNALVA DE SOUZA PEREIRA LIMA

Uma banca de QUALIFICAÇÃO de MESTRADO foi cadastrada pelo programa.
STUDENT : EDNALVA DE SOUZA PEREIRA LIMA
DATE: 28/04/2023
TIME: 14:00
LOCAL: Plataforma online
TITLE:

Evaluation of the effects of medicines containing Cannabis sativa on the acitivity of the Cytochrome P450(3A4) in Wistar rats

KEY WORDS:

Cannabis sativa; tetrahydrocannabidiol; cannabidiol, pharmacokinetic interaction; cytochrome P450

PAGES: 46
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUBÁREA: Análise e Controle de Medicamentos
SUMMARY:

Reports about the use of products derived from Cannabis sativa for religious, medicinal and recreational purposes date back more than two thousand years. Among the various phytochemicals present in this species, tetrahydrocannabinol (THC) and cannabidiol (CBD) should be highlighted. THC has antiemetic, antispasmodic, analgesic, and appetite-stimulating activities. CBD, on the other hand, has indications for the treatment of refractory epilepsy, anxiety, psychotic and pain disorders. Patients who need to use Cannabis-derived products have chronic illnesses and usually use the phytoderivative in association with several other conventional medications, increasing the risk of possible interactions. Studies involving the interaction of Cannabis-derived products with conventional medicines are scarce and contradictory. The objective of this work was to evaluate in vivo the effects of products containing Cannabis sativa commercially available in Brazil on the activities of the cytochrome P450 3A system (CYP 3A), the main metabolic pathway of drugs. For this, midazolam (MDZ) was used as a marker of the activity of this enzyme. The pharmacokinetic profile of  MDZ  (20 mg.kg^-1) was determined  in the absence and presence of the commercial product CBD (20 mg.mL^-1; 20 mg.kg^-1) and the medicinal oil of THC and CBD (15 mg.mL^-1; 20 mg.kg) in Wistar rats. Blood collections were performed at predetermined times. Plasma MDZ levels were quantified using a previously validated method using the HPLC technique, from which the following pharmacokinetic parameters were determined: plasma half-life (t_1/2), total clearance (Cl/F), area under the curve of plasma concentration versus time (AUC), maximum plasma concentration (C_max) and time to reach C_max (t_max) and relative bioavailability (F_r). The Cannabis-derived products increased the AUC_(0-6h) and C_max  4- and 10-fold, respectively. The results suggest a probable enzymatic inhibition, which may compromise the pharmacological response of the drugs metabolized via  CYP3A in clinically relevant manner. Additional studies will be performed to confirm these results and to reduce interindividual variability.

BANKING MEMBERS:
Interno - 1300132 - WHOCELY VICTOR DE CASTRO
Interno - 1150851 - RENE OLIVEIRA DO COUTO
Externo ao Programa - 1908201 - JOAQUIM MAURICIO DUARTE ALMEIDA
Externa ao Programa - 1971548 - CRISTINA SANCHES