Kajian Nefrotoksik, Hepatotoksik, dan Kardiotoksik Akibat Penggunaan Parasetamol Bersama Kafein pada Kelinci

Abstract

Paracetamol (PCT) is widely used as analgesic and antipyretic. But based on the clinical data had been reported nefrotoxicity, hepatotoxicity, and cardiotoxicity following ingestion of PCT. This thing resulted by toxic metabolite paracetamol in the form of N-acetyl-P-benzoquinoneimine (NAPQI) which can be enhanced by caffeine. Related to the statement mentioned above, the influence of caffeine consumption with PCT has been studied to prove hepatotoxicity, nephrotoxicity, and cardiotoxicity by determining pharmacokinetic parameters such as maximum concentration (Cmax), Area Under the Curve (AUC), Clearance (Cl), and elimination half life (t½ elimination) and also determining serum creatinine levels. Besides that the image of histopathologic kidney, heart and liver also observed. The study was experimental method by using healthy male rabbit and weight 1 - 2 kg as. PCT and caffeine also PCT alone without caffeine were given as single dose, , then at minute 0, 15, 30, 60, 90, 120, 150, 210, 270, 510 dan 630 blood is collected for determination of pharmacokinetic parameters, and folowe by ingestion PCT alone and also with caffeine three times a day for three days, with PCT in three dose variations were 23, 46, and 69 mg/kg BW while caffeine in fixed dose 3 mg/kg BW; at the third day blood is collected for determination of serum creatinine levels after treatment. After blood having collected, animal were killed then cut opened; and kidney, heart and liver were collected for histopatologically examination. Based on the result of the research it was found that caffeine altered pharmacokinetic parameters of PCT. The change of Cmax, AUC, and Cl, in various dose PCT statisticly significant different · (P>0.05; n=6). While the change t½ elimination non-significant different (P>0.05; n=6). Increasing of dose PCT also alter pharmacokinetic parameters of PCT significant (P>0.05; n=6). Level serum creatinine which measured were found improvement at group of combination PCT and caffeine, also at increasing of dose PCT but statisticly non-significant different (P>0.05; n;6) and also still in normal value. Histology observation at preparative kidney, liver, and heart that given PCT with caffeine and also increasing of dose PCT making worse damage of kidney, heart and liver in the form tubulus dilatation, damage of glomerulus, and damage of cytoplasm at kidney; sinusoid dilatation and damage of cytoplasm at liver; and also estrange of tissues and damage of cytoplasm at heart. This suggested that combination PCT with caffeine and also the increasing of dose PCT will increase nefrotoxic, hepatotoxic, and cardiotoxic PCT.