Effect of Nigella sativa oil on pharmacokinetics and pharmacodynamics of gliclazide in rats

Abstract

Nigella sativa oil (NSO) has been used widely for its putative anti‐hyperglycemic activity. However, little is known about its potential effect on the pharmacokinetics and pharmacodynamics of antidiabetic drugs, including gliclazide. This study aimed to investigate herb–drug interactions between gliclazide and NSO in rats. Plasma concentrations of gliclazide (single oral and intravenous dose of 33 and 26.4 mg/kg, respectively) in the presence and absence of co‐administration with NSO (52 mg/kg per oral) were quantified in healthy and insulin resistant rats (n = 5 for each group). Physiological and treatment‐related factors were evaluated as potential influential covariates using a population pharmacokinetic modeling approach (NONMEM version 7.4). Clearance, volume of distribution and bioavailability of gliclazide were unaffected by disease state (healthy or insulin resistant). The concomitant administration of NSO resulted in higher systemic exposures of gliclazide by modulating bioavailability (29% increase) and clearance (20% decrease) of the drug. A model‐independent analysis highlighted that pre‐treatment with NSO in healthy rats was associated with a higher glucose lowering effect by up to 50% compared with that of gliclazide monotherapy, but not of insulin resistant rats. Although a similar trend in glucose reductions was not observed in insulin resistant rats, co‐administration of NSO improved the sensitivity to insulin of this rat population. Natural product–drug interaction between gliclazide and NSO merits further evaluation of its clinical importance.

INFLUENCE OF Momordica charantia (L.) ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF GLICLAZIDE IN ALLOXAN-INDUCED DIABETIC RATS

“…In direct observation, the tmax values were obtained for the single gliclazide administration group and the group given together with BME, which were approximately half an hour or 30 minutes after the rats were given the drug. These results were faster than those of previous studies, which stated that the tmax of gliclazide occurred 1-2 hours after drug administration (Adiwidjaja and Sasongko, 2021). In addition, it can be seen that the maximum plasma gliclazide concentration (Cmax) in the group given gliclazide together with BME only reached half of the Cmax in the group given gliclazide alone.…”

“…Urethane was administered intravenously. At the end of the experiment, the rats were euthanized by administering high doses of urethane (Adiwidjaja and Sasongko, 2021).…”

“…In a previous study conducted by Adiwidjaja and Sasongko (2021), the pharmacokinetic profile of gliclazide followed two-compartment oral kinetics, either in the gliclazide group administered alone or in the gliclazide group co-administered with herbs. Two-compartment modeling more accurately describes the profile of gliclazide because the concentration of gliclazide in the plasma decreases biphasically or in two phases.…”

An effective ultra‐performance liquid chromatography and derivatization method for the quantification of potential genotoxic impurity Hydrazine in Gliclazide and its formulation – Robustness study by the design of experiments

“…Reported F I G U R E 1 Chemical Structures of Gliclazide (GLZ) and Hydrazine (HNE) hydrate additional beneficial pharmacological properties of GLZ, including immunomodulatory and anticoagulant activities, suggested its potential application in treating type 1 diabetes mellitus [13,14]. It is an oral anti-hyperglycemic agent used to treat non-insulin-dependent diabetes mellitus and may have the additional advantage of potentially slowing the progression of diabetic retinopathy [15]. GLZ is marketed typically as tablet oral dosage forms under trade names with different tablet strengths such as Azukon-30, 80 mg; Diabend-30, 80 mg; and Glizid-40, 60, and 80 mg. GLZ is also combined with other pharmaceutical ingredients like GLZ and Metformin., GLZ, Metformin, and Pioglitazone.…”