Gliclazide In Rabbits Research Articles

Influence of Eugenol on the Pharmacokinetics and Pharmacodynamics of Gliclazide in rabbits

Diabetes is the most prevailing health disorder with high mortality rate and showing increased health costs across the globe. World Health Organization has claimed that lifestyle changes are one of the major causes of diabetes in this modern living. Gliclazide is an oral antidiabetic drug that is taken by majority of patients suffering with type-2 diabetes. With the increased awareness of nutraceuticals in health care management, many patients are consuming them. Hence, in the present investigation it is sought to determine the pharmacokinetic and pharmacodynamic interactions of gliclazide with eugenol in diabetic induced rabbits. Streptozotocin was used for inducing diabetes in healthy rabbits. Four different groups, each with 6 rabbits, are taken in the study. Group A is diabetic control, Group B is treated with gliclazide alone, Group C is treated with eugenol alone and Group D is treated with combination of gliclazide and eugenol. The results clearly indicated that there is an advantage in both pharmacokinetic and pharmacodynamic parameters with combination therapy of gliclazide and eugenol in diabetic rabbits.

Influence of aprepitant on the pharmacodynamics and pharmacokinetics of gliclazide in rats and rabbits.

BackgroundConcomitant drug administration is a general phenomenon in patients with chronic diseases such as diabetes mellitus. Among the currently available oral antidiabetic drugs, gliclazide is a commonly prescribed drug considering its multiple benefits in diabetic patients. Aprepitant is a commonly prescribed antiemetic drug which is mainly metabolized by CYP3A4, reported to have modest inductive and inhibitory effects on CYP2C9 and CYP3A4, respectively. Since gliclazide is metabolized by CYP2C9 (major) and CYP3A4 (minor), it is very difficult to predict the influence of aprepitant and its metabolic interaction with gliclazide. Considering the complexity associated with the combination of aprepitant and gliclazide, this study was designed to evaluate the influence of aprepitant on the pharmacodynamics (PD) and pharmacokinetics (PK) of gliclazide in animal models.MethodsThe PD interaction studies were conducted in both rodent (normal and alloxan-induced diabetic rats) and non-rodent (rabbits) animal models (n = 6) while the PK interaction study was conducted in normal rabbits (n = 6). An extrapolated human therapeutic oral dose of gliclazide, aprepitant and their combination were administered to rats and rabbits with 7 days washout between each treatment. For the multiple-dose interaction study, the same groups were administered with an interacting drug (aprepitant) for 7 days and then the combination of aprepitant and gliclazide on the 8th day. From the collected animal blood samples, blood glucose (by Glucose-Oxidase/Peroxidase method), insulin (by ELISA method) and gliclazide concentration levels (by HPLC method) were determined. Non-compartmental PK analysis was conducted by Phoenix WinNonlin software to determine the PK parameters of gliclazide. Statistical analysis was performed by student’s paired t-test.ResultsThe pharmacodynamic activity (blood glucose reduction and insulin levels) of gliclazide was significantly (p < 0.05) influenced by aprepitant in normal and diabetic condition without any convulsions in animals. There was a significant (p < 0.05) increase in concentration levels and Area Under the Curve of gliclazide while significant (p < 0.05) decrease in clearance levels of gliclazide in rabbits. The PK interaction with gliclazide is relatively more with the multiple dose treatment of aprepitant over single dose treatment.ConclusionIn combination, aprepitant significantly influenced the pharmacodynamic activity of gliclazide in animal models. Considering this, care should be taken when this combination is prescribed for the clinical benefit in diabetic patients.

Influence of Efavirenz and Nevirapine on the Pharmacodynamics and Pharmacokinetics of Gliclazide in Rabbits

Background : Since polypharmacy is very common practice in diabetic patients, the study of drug-drug interactions is an imperative rational approach with respect to safety and efficacy determination. Gliclazide is a widely used drug for the treatment of type 2 diabetes. Efavirenz and nevirapine are widely used non-nucleoside reverse transcriptase inhibitors (NNRTIs) with fewer side effects concerning diabetic complications.The objective of the study is to investigate the effect of selected NNRTIs on the pharmacodynamics and pharmacokinetics of gliclazide in rabbits with respect to safety and efficacy of the combination. Methods : Influence of selected NNRTIs on the activity of gliclazide was determined by conducting a single dose interaction followed by multiple dose interaction study with two groups consisting of 6 normal rabbits each. Each group was treated with an oral dose of 5.6 mg/1.5 kg bd. wt. of gliclazide, interacting drug treatment (42 mg/1.5 kg bd. wt. of efavirenz or 14 mg/1.5 kg bd. wt. of nevirapine) and their combination with a one week washout period between each treatment. One week washout after this single dose interaction study, each group was continued with the daily treatment of interacting drug for the next eight days and then the combined treatment on the ninth day. Blood samples were collected at regular intervals by marginal ear vein puncture in rabbits and were analyzed for blood glucose by GOD/POD method and insulin by radioimmunoassay method. The serum gliclazide levels were estimated by HPLC method and pharmacokinetic analysis was conducted by noncompartmental analysis using WinNonlin software. Results : In combination, efavirenz significantly (P less than 0.05) reduced the pharmacodynamic activity and serum levels of gliclazide. The pharmacokinetic parameters of gliclazide were significantly (P less than 0.05) altered. The percent decrease of serum gliclazide concentration level is 24.23% and 15.20% following single dose and multiple dose administration of efavirenz, respectively. In combination, nevirapine has no significant effect on the pharmacodynamics and pharmacokinetics of gliclazide in rabbits. Conclusions : The significant pharmacokinetic interaction of efavirenz at metabolic level by CYP3A4 induction results in decreased serum gliclazide levels and pharmacodynamic activity of gliclazide. The combination of nevirapine and gliclazide was proved to be safe. doi:10.4021/jem34w

Effect of protease inhibitors (indinavir and ritonavir) on the pharmacokinetics of gliclazide in rabbits

The objective of this study was to investigate the effect of protease inhibitors (indinavir and ritonavir) on the pharmacokinetics of gliclazide in rabbits and to evaluate the mechanism of interaction of the combination. Studies in rabbits were conducted with oral doses of gliclazide, selected protease inhibitor, and their combination with a 1-week washout period between each treatment (single dose followed by multiple dose treatment). Blood samples were collected at regular time intervals by marginal ear vein puncture and serum gliclazide levels were analyzed by high-pressure liquid chromatography. Pharmacokinetic analysis was performed by noncompartmental analysis using WinNonlin Software. In combination, ritonavir significantly increased serum gliclazide levels and altered the pharmacokinetic parameters of gliclazide in rabbits while indinavir had no significant effect. The percentage increase of serum gliclazide level was 22.34% and 27.78% following single-dose and multiple-dose treatment of ritonavir, respectively. The interaction of ritonavir with gliclazide is pharmacokinetic at a metabolic level (by CYP3A4 inhibition) in normal rabbits, while the interaction of indinavir with gliclazide is pharmacodynamic, which needs dose adjustment, and care should be taken when these

Influence of Efavirenz and Nevirapine on the Pharmacodynamics and Pharmacokinetics of Gliclazide in Rabbits

Influence of Efavirenz and Nevirapine on the Pharmacodynamics and Pharmacokinetics of Gliclazide in Rabbits

Influence of an Aqueous Extract of Azadirachta indica Leaf on the Pharmacodynamics and Pharmacokinetics of Gliclazide in Rats and Rabbits

In diabetes, optimal blood sugar control is needed to maintain health. Both allopathic and herbal drug therapy medicinal plants are being used in therapy for diabetes, but interactions between these two types of medicine are unknown. To determine whether an herbal drug (the aqueous extract of Azadirachta indica leaves) altered the effects of allopathic treatment (gliclazide) of diabetes, this study monitored blood sugar in non-diabetic and diabetic rats and non-diabetic rabbits treated with gliclazide, A. indica extract, and a combination of these two drugs. Hypoglycemia in normal and diabetic rats reached a peak at 1 hour and 8 hours and in rabbits at 3 hours after administration of gliclazide. Administration of A. indica extract reduced blood sugar when given alone and prolonged the effect of gliclazide more than 8 hours in non-diabetic rats, beyond 12 hours in diabetic rats, and more than 8 hours in non-diabetic rabbits without hypoglycemic convulsions. The presence of A. indica extract did not alter the pharmacokinetics of gliclazide in rabbits. This study indicated that the combination of gliclazide and A. indica can be used safely to get prolonged and sustained antidiabetic effects.