Histological and Biochemical Markers on the Liver of Male Albino Rats on Oral Administration of Nevirapine
CHAPTER ONE
Objectives of the study
The main objective of the study is to examine the histological and biochemical markers on the liver of male albino rats on oral administration of Nevirapine.
CHAPTER TWO
LITERATURE REVIEW
Nevirapine
Patents
US patent no. 5366972 gives information for the preparation of novel 5, 11-dihydro-6Hdipyrido [3,2-b:2,3-e][1,4] diazepine i.e. Nevirapine and use of these compounds in the prevention or treatment of HIV infection.
US patent no. 8212025B2 describes the improved process for the preparation of Nevirapine with good quality and purity. It also describes various methods for the production of commercial scale drug substance.
US patent no. 20100278918 provides information about pharmaceutical composition for the preparation of Nevirapine ER tablets and its method of manufacturing. The rate controlling polymer used for the preparation of ER tablet is HPMC. It also gives information about in vivo bio-availability of different strengths of Nevirapine and dependent and independent claims.
US patent no. 6680383B1 gives information about manufacturing process of Nevirapine. It also describes the concentration of intermediates for the preparation of final drug substance. Patent claims the method of manufacturing of drug substance.
Publish Literature Review
Iris Usach et al. describe the bioavailability of Nevirapine in rats after oral and subcutaneous administration, in vivo absorption from gastrointestinal segments and effect of bile on its absorption from duodenum. It also provides the information about the method of analysis and statistical conclusion of the study.
Kappelhoff B.S. et al. give information about pharmacokinetics of Nevirapine once-daily versus twice-daily dosing in the 2NN study. They also describe in vivo performance of once-daily Nevirapine. They give the details of the in vivo study design. The daily exposure to Nevirapine (AUC24h) was similar for the 400 mg once-daily and the 200 mg twice-daily dosing regimens. The Cmin of Nevirapine is lower and the Cmax of Nevirapine is higher for the once-daily regimen as compared to the twice-daily regimen.
CHAPTER THREE
MATERIALS AND METHODS
Animals
Fifteen male adult wistar rats were obtained from a breeding stock maintained in the animal house of the Agricultural Science Department, Ladoke Akintola University of Technology (LAUTECH), Ogbomoso, and housed in well ventilated plastic cages in animal house in Department of Pure and Applied Biology, LAUTECH, Ogbomoso. The rats were maintained under standard natural photoperiodic condition of twelve hours of light alternating with twelve hours of darkness (i.e. L:D;12h:12h photoperiod) at room temperature, allowed unrestricted access to water and rat chow and acclimatized for 7 days before the commencement of the experiment. The body weights of the rats ranged between 180 and 300g.
CHAPTER FOUR
RESULTS AND DISCUSSION
Results
The mean body weight gain of the rats treated with antiretroviral drug as shown in Table 1 has no significant differences when compared with the control group that received distilled water and food for 6 weeks.
Table 2 shows significant differences in ALP, AST and ALT. AST and ALT mean values increased as compared to the control, however, ALP mean value decreased when compared with the control.
CHAPTER FIVE
CONCLUSION
The above results suggest that NVP administration may cause liver hepatotoxicity in albino wistar rats.
The effect of antiretroviral drugs on biochemical indices of liver function is of paramount importance and should not be overlooked. This is to ensure that the liver function is not impaired in the process of managing a particular health problem in case of HIV patient, hoping to minimize the duplication of this virus in the human system, while a lot of harm is being done to the liver. The observation that it takes some weeks to develop liver injury means that NVP itself plays a role in the initiation of the lesion. Therefore, it can be concluded that NVP activates the cell-mediated immune response leading to liver injury that is propagated by the drug itself or the immune system.
Following the results in this study and various reports on related studies, it could be concluded that the lives of HIV patients on regular use of HAART containing Nevirapine are prone to risk.
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