Effect of Sijunzi Pills on Pharmacokinetics of Omeprazole in Beagle Dogs by HPLC-UV: A Herb-Drug Interaction Study

Abstract

A sensitive high-performance liquid chromatography (HPLC-UV) method for determination of omeprazole in beagle dog plasma was developed and to investigate the effect of Sijunzi pills (SJZPs) on the pharmacokinetics of omeprazole in beagle dogs. The beagle dog plasma was extracted with ethyl acetate and n-hexane under alkaline conditions. Omeprazole and internal standard (IS, fluconazole) were separated on an XDB-C18 column, and acetonitrile and 0.1% trifluoroacetic acid were used as the mobile phase. Omeprazole and IS were detected by using a diode array detector. This experiment adopts the experimental design of double-cycle self-control. In the first cycle (group A), six beagle dogs were given omeprazole 0.67 mg/kg orally in a single dose. In the second period (group B), the same six beagle dogs were orally given SJZPs 0.2 g/kg twice a day for 7 consecutive days, and then, omeprazole was orally given. At the different time points after omeprazole was given in the two periods, the blood samples were collected. The concentration of omeprazole was detected by the developed HPLC method. DAS 2.0 was used to calculate the pharmacokinetic parameters of omeprazole. Under the current experimental conditions, this UPLC method showed good linearity in the detection of omeprazole. Interday and intraday precision did not exceed 10%, and the range of accuracy values were from −1.43% to 2.76%. The results of extraction recovery and stability met the requirements of FDA approval guidelines of bioanalytical method validation. The Cmax of omeprazole in group B was 61.55% higher than that in group A, and the AUC(0−t) and AUC(0−∞) of omeprazole in group B were 63.96% and 63.65% higher those that in group A, respectively. At the same time, the clearance (CL) and apparent volume of distribution (Vd) decreased in group B. In this study, an HPLC method for the determination of plasma omeprazole concentration was established. SJZPs could inhibit the metabolism of omeprazole and increase the concentration of omeprazole in beagle dogs. It is suggested that when SJZPs are combined with omeprazole, attention should be paid to the herb-drug interactions and possible adverse reactions.

Pharmacokinetics of Herb-Drug Interactions of Plumbagin and Tazemetostat in Rats by UPLC-MS/MS

“… 24 Sijunzi pills could inhibit the metabolism of omeprazole and increase the concentration of omeprazole in beagle dogs. 25 …”

“…24 Sijunzi pills could inhibit the metabolism of omeprazole and increase the concentration of omeprazole in beagle dogs. 25 Tazemetostat is a first-in-class small molecule enhancer of EZH2 inhibitor. 11 The most common treatment-related adverse events (AEs) were asthenia, anemia, anorexia, muscle spasms, nausea, and emesis, which were mostly grade 1 or 2 in severity.…”

Effect of Chaihu Shugan Pills on the Pharmacokinetics of Duloxetine and its Metabolite 4-Hydroxyduloxetine in Beagle Dogs: A Herb-Drug Interaction Study

“…Our previous research results showed that Danzhi Xiaoyao pills can accelerate the metabolism of venlafaxine in beagle dogs, reduce the plasma exposure of venlafaxine, and increase the content of O-desmethylvenlafaxine (ODV) and N-desmethylvenlafaxine (NDV) [ 19 ]. Sijunzi Pills could inhibit the metabolism of omeprazole and increase the concentration of omeprazole in beagle dogs [ 18 ].…”

“…e main methods used to detect duloxetine hydrochloride were HPLC [13] and LC-MS [14][15][16]. UPLC-MS/MS technology was a common method for drug-drug interactions (DDIs) and herb-drug interactions (HDIs) [17][18][19](Ruan et al; Xia et al, 2021;Zhu et al, 2019). So, in this study, we optimized the methodology according to the concept and principles of Green Analytical Chemistry (GAC) [20] and established a UPLC-MS/MS for the simultaneous determination of duloxetine as well as its metabolite 4-hydroxyduloxetine in beagle dog plasma.…”