Exploring Drug-Drug Interactions between Losartan and Carbamazepine: A Pharmacokinetic and Pharmacodynamic Study.

Abstract

Background: Hypertension, which affects 1.28 billion people globally aged 30 to 79, is characterized by continuously high blood pressure (140/90 or more) and raises the risk of premature death. Losartan, an angiotensin receptor blocker (ARB), is suggested for patients under the age of 55 who cannot take ACE inhibitors as a first treatment option. Epilepsy, a chronic neurological illness marked by repeated seizures, affects more than 50 million individuals worldwide and is the third most common chronic brain disorder. Both hypertension and epilepsy are frequent chronic illnesses, with increased blood pressure greatly raising the risk of epilepsy due to its relationship with cerebrovascular disease, doubling the risk when compared to people with normal blood pressure.

Objective: The effect on pharmacokinetics and pharmacodynamics of losartan on concomitant administration with carbamazepine was investigated.

Materials and methods: Wistar rats of either sex, with a minimum of six animals per group, were used in the investigation. The rats were treated with Losartan and Losartan-Carbamazepine for 30 days. Blood samples were taken via retro-orbital plexus at 0, 1, 2, 4, 6, and 12 hours after treatment concluded, and they were subjected to high-performance liquid chromatography for plasma analysis to calculate AUC, t1/2, and Clearance. A pharmacodynamic evaluation was done by inducing hypertension in rats using a 10% fructose solution and the effect of pretreated Losartan and Losartan-Carbamazepine on blood pressure was determined.

Results: In the Losartan and Carbamazepine treated group, there was a reduction in the AUC and t1/2 and a reported increase in the clearance value compared to Losartan alone treated rats. In fructose-induced hypertension model to evaluate the effect of losartan and carbamazepine on BP showed an increase in mean arterial pressure, plasma glucose, and a reduction in triglycerides level was noted in comparison to Losartan alone treated rats indicating therapeutic failure of Losartan.

Conclusion: Based on these studies, it is concluded that CBZ has reduced the effectiveness of losartan and therefore, co-administration of these drugs should be avoided.