Pharmacokinetic and pharmacodynamic drug interactions of carbamazepine and glibenclamide in healthy albino Wistar rats

Prashanth, S; Kumar, Abhiram; Madhu, B; Rama, Nona; Sagar, J Vidya

doi:10.4103/0976-500x.77083

Cited by 8 publications

(4 citation statements)

References 11 publications

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“…Healthy rat model served to quickly identify the interaction. 11 In the present study we studied the influence of ornidazole on the pharmacodynamics and pharmacokinetics of gliclazide. Ornidazole enhanced the hypoglycaemic activity of gliclazide on multidose treatment (31.962 ± 5.4 to 40.032 ± 5.5) at second hour however it is found to be statistically non-significant.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Interaction of Gliclazide with Ornidazole in Healthy Albino Wistar Rats

Thumuganti¹,

Mada²,

Meesa³

et al. 2015

JYP

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Background: Gliclazide is a widely used drug for the treatment of type 2 diabetes. Retrospective studies shows that diabetics are at increased risk of suffering severe complications after amoebic infection. Ornidazole is a widely used antiamoebic drug. The objective of this study was to examine the effect of oral administration of ornidazole on blood glucose levels, investigate its effect on the activity and pharmacokinetics of gliclazide in normal rats and to evaluate the safety and effectiveness of the combination. Methods: Studies in normal rats were conducted with oral doses of 2 mg/kg body weight of gliclazide and 25 mg/kg body weight of ornidazole andin combination. Blood samples were collected at regular time intervals from rat's orbital sinuses. All the blood samples were analysed for blood glucose by glucose oxidase/peroxidase (GOD/POD) method and HPLC was used to understand the pharmacokinetics of gliclazide alone and in combination with ornidazole. Results: The results of the present study is indicating that ornidazole does not possess glucose lowering activity therefore it may be inferred that drug-drug interaction of ornidazole with gliclazide is pharmacokinetic type and the possible interaction may be due to CYP2C9 inhibition. Gliclazide produced glucose lowering activity in normal rats with peak activity at 2 h. In combination, ornidazole increases the effect of gliclazide in rats. Conclusion: Thus, it can be concluded that the combination of ornidazole and gliclazide may need slight dose adjustment and care should be taken when the combination is prescribed for their clinical benefit in diabetic patients. However, further studies are warranted.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Interaction of Gliclazide with Ornidazole in Healthy Albino Wistar Rats

Thumuganti¹,

Mada²,

Meesa³

et al. 2015

JYP

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“…The required quantity of CBZ was then added to prepared FA solution and left for 48 h. The sample was then frozen overnight and lyophilized using 2% w/v sucrose as a cryoprotectant. The obtained mass was powdered using a glass mortar-pestle and passed through 100-mesh sieve [14,19,20].…”

Section: Preparation Of Complexmentioning

confidence: 99%

“…The animals were dosed similarly to the pharmacokinetic protocol, 30 min before the induction of MES. A strain was applied using an electro-convulsiometer (Techno India, Lucknow, India) using the following conditions: 150 mA, 0.2 s, and average voltage 200-250 V. The incidence and duration of seizures (tonic-clonic convulsions) were recorded [19].…”

Section: Pharmacodynamic Study/mes (Maximal Electroshock)-induced Con...mentioning

confidence: 99%

Quality and In Vivo Assessment of a Fulvic Acid Complex: A Validation Study

et al. 2022

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The present work aimed to re-assess the bioavailability enhancement potential of fulvic acid (FA). Carbamazepine (CBZ) and peat were used as a model drug and FA source, respectively. Our group has already evaluated the bioavailability enhancement potential of a less commercially viable source of FA, i.e., shilajit. In the present work, the phase solubility of CBZ was analyzed with varying concentrations of peat-sourced FA (2–12% w/v). The prepared complex (CBZ-FA) was characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Dissolution, pharmacokinetic, and pharmacodynamic studies were also carried out. The results showed the presence of an interaction between the drug and FA within the complex, which led to 98.99 ± 2.0% enhancement in drug solubility. The results also showed 79.23 ± 2.1% dissolution of the complexed drug over 60 min and 69.32 ± 2.2% permeation from the intestinal gut sac over 90 min, which led to a significant enhancement of bioavailability and a reduction in the duration of epileptic seizures. Thus, this study re-authenticates our earlier results and suggests switching the FA source (shilajit to peat) for commercial product development.

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“…Many clinically used drugs such as paclitaxel, 8) fexofenadine, 9) and oseltamivir 10,11) have been recognized as P-gp substrates, and thus, P-gp has received considerable attention as a potential determinant of the oral bioavailability of its substrates in humans and animals. [12][13][14][15][16] Double-peaks of plasma concentration have often been observed following oral administration of P-gp substrates to humans and experimental animals. The double-peak is thought to result from various factors, among which inter-segmental variation of P-gp activity along the small intestine is considered important.…”

Section: Introductionmentioning

confidence: 99%

The Role of Inter-segmental Differences in P-glycoprotein Expression and Activity along the Rat Small Intestine in Causing the Double-peak Phenomenon of Substrate Plasma Concentration

Wada

Kano

Mita

et al. 2013

Drug Metabolism and Pharmacokinetics

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Conflicting results have been reported on segmental differences in expression of P-glycoprotein (P-gp) along the small intestine of animals and humans. In this study, we investigated P-gp mRNA and protein levels within each of nine segments of rat small intestine. In addition, P-gp activity in each segment was evaluated in terms of permeability of rhodamine123 (Rho123), a typical P-gp substrate, using the serial intestinal non-everted sac method. The P-gp mRNA levels tended to increase from the duodenum to the ileum, with peaks in the upper and lower ileum, while P-gp protein level reached its maximum in the middle ileum. The activity of P-gp was also the highest in the middle ileum, and was highly correlated with P-gp protein level. The double-peaked plasma concentration profile that was observed following oral administration of Rho123 to rats could be well reproduced by an intestinal compartmental kinetic model incorporating inter-segmental differences of absorption and excretion rate constants. Our results suggest that the heterogeneous distribution of P-gp along the small intestine plays a key role in causing the double-peak of plasma concentration of P-gp substrates following oral administration to rats.

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Pharmacokinetic and pharmacodynamic drug interactions of carbamazepine and glibenclamide in healthy albino Wistar rats

Cited by 8 publications

References 11 publications

Pharmacokinetic Interaction of Gliclazide with Ornidazole in Healthy Albino Wistar Rats

Pharmacokinetic Interaction of Gliclazide with Ornidazole in Healthy Albino Wistar Rats

Quality and In Vivo Assessment of a Fulvic Acid Complex: A Validation Study

The Role of Inter-segmental Differences in P-glycoprotein Expression and Activity along the Rat Small Intestine in Causing the Double-peak Phenomenon of Substrate Plasma Concentration

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