Pharmacokinetic interaction study between flavanones (hesperetin, naringenin) and rasagiline mesylate in wistar rats

Abstract

Cytochrome P-450 (CYP) enzymes and P-glycoprotein (P-gp) play an important role in the oral bioavailability and first-pass-metabolism (FPM) of many drugs. Rasagiline is a selective, monoamine oxidase-B inhibitor and it undergoes significant FPM in the liver prior to excretion by CYP1A2. Hesperetin and naringenin are naturally occurring flavanones and are reported as modulators of CYP enzymes and P-gp. The objective of the present investigation was to evaluate the effect of hesperetin and naringenin on the pharmacokinetics (PK) of rasagiline in rats. Rats were treated orally with rasagiline (2 mg/kg) alone and co-administered with hesperetin and naringenin (12.5 and 25 mg/kg) for 15 consecutive days. Blood samples were collected from tail vein on the 1st day in a single dose PK study (SDS) and on 15th day in the multiple dose PK study (MDS). Hesperetin and naringenin co-administration significantly enhanced the area under the curve (AUC), maximum plasma concentration (Cmax) and elimination half life (t1/2) of rasagiline with a concomitant reduction in clearance (CL/F) in both SDS and MDS. Rasagiline concentrations were significantly increased when co-administered with hesperetin and naringenin in the brain. No significant difference was found in rasagiline transport from mucosal to serosal side in the presence of hesperetin and naringenin ex vivo (rat everted gut sacs used). Our findings suggested that hesperetin and naringenin enhanced the systemic exposure of rasagiline might be through the inhibition of CYP1A2 but not P-gp. Further studies are needed on CYP1A2 and P-gp over expressed cells to confirm this interaction at cellular level.

Effects of naringenin on the pharmacokinetics of tofacitinib in rats

“…At the same time, herbs may also affect CYP450 enzymes, and the flavonoids are among the most important. Hesperetin can affect CYP1A2, and quercetin can affect CYP3A4, CYP2C9, CYP1B1 and CYP1A1 (Chen et al 2009;Pingili et al 2016;Jana and Rastogi 2017;Palle and Neerati 2018). Naringenin is an aglycone of naringin; it has previously been reported that naringenin can inhibit CYP3A4 (Liu J et al 2019).…”

Potencial antihiperglicémico de Gentianella gilgiana (Reimers) Fabris ex J.S. Pringle en la absorción intestinal de glucosa in vitro en ratas albinas diabéticas

“…Se lavó con solución salina fisiológica fría. Para la eversión del intestino, se siguió la técnica descrita por Wilson y Wiseman (17) y reproducida por otros investigadores (18)(19)(20) , que fue modificada para este estudio, reemplazando el material de la varilla, que era de acero inoxidable, por polietileno, con aumento ligero de la longitud (Figura 2). Inmediatamente después de extraer la pieza de intestino y everterla con una varilla de polietileno (1,5 mm, 350 mm), se colocó en una placa petri con solución salina, adecuada oxigenación y temperatura a 37 °C.…”

ABCB1: is there a role in the drug treatment of Parkinson’s disease?

“…In this regard, it is noteworthy, that the ABCB1 function weakening verapamil is well known as onset of idiopathic PD onset facilitating or PD syndrome inducing compound [7]. There is no interaction between ABCB1 function and the MAO-B inhibiting compounds selegiline, rasagiline, and safinamide [9,10]. All of them reduce oxidative stress.…”