Pakistan J. Zool., vol. 42(4), pp. 395-400, 2010. Comparison of Bioavailability and Pharmacokinetics of Diclofenac Sodium and Diclofenac Potassium in Healthy and Escherichia coli Induced Febrile Rabbits Mahmood Ahmad, Muhammad Iqbal, Naveed Akhtar, Ghulam Murtaza * , Muhammad Asadullah Madni and Fatima Rasool Department of Pharmacy, Faculty of Pharmacy and Alternative Medicines, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan (MA, NA, GM, MAM, FR), and Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan (MI) Abstract.- Diclofenac sodium and diclofenac potassium in tablet dosage form were tested for their bioavailability and disposition kinetics in a group of 18 rabbits in normal and Escherichia coli induced febrile condition with a washout period of 7 days. Biochemical and physiological parameters were measured in both normal and febrile state. Diclofenac levels in plasma were determined using a reversed-phase HPLC method. Primary kinetic parameters i.e. AUC 0-∞ , C max , t max and other disposition kinetics, were obtained with non-compartmental procedure. The values of physiological and biochemical parameter were significantly (p<0.05) low in febrile rabbits as compared to that of normal animals. The drug concentration levels and pharmacokinetics of orally administered diclofenac sodium and diclofenac potassium were changed during fever. The comparison of diclofenac sodium and diclofenac potassium in normal and febrile conditions showed significantly (p<0.05) increased level of diclofenac potassium in both conditions normal & febrile. Keywords: Diclofenac sodium, diclofenac potassium, endotoxin induced fever, bioavailability, disposition kinetics. INTRODUCTION Non-steroidal anti-inflammatory drugs (NSAIDs) are heterogeneous compounds often chemically unrelated (although most of them are organic acids), which nevertheless share certain therapeutic action and side effects. Their therapeutic activity appears to depend on large extent upon the inhibition of defined biochemical pathway responsible for the biosynthesis of prostaglandins and other related autacoids. NSAIDs have different spectrum of activity than do the analgesics. They have anti-inflammatory, antipyretic and analgesic effects. In general these agents are most effective in pain associated with inflammation such as arthritis (Martindale, 2002). Diclofenac possesses structural characteristics of arylalkanoic acid agents and display anti-inflammatory, analgesic and anti- pyretic properties (Dreve et al., 2009). In the carrageen an induced rat paw edema assay, it is twice as potent as indomethacin and 450 times as * Corresponding author: gmdogar356@gmail.com 0030-9923/2010/0004-0395 $ 8.00/0 Copyright 2010 Zoological Society of Pakistan. potent as aspirin (Van Miert and Van Goghham, 1976). As an analgesic, it is 6 times more potent than indomethacin and 40 times more potent than aspirin in the phenyl-benzoquinone induced writhing assay in mice. As an anti-pyretic it is twice as potent as indomethacin and over 350 times as potent as aspirin in yeast induced fever assay in rats (Munir et al., 2007; Van Gogh and Van Miert, 1977). Fever is a condition in which body temperature is higher than normal i.e. 37°C (Roth et al., 2006). The cause of fever is pyrogens secreted by toxic bacteria or pyrogens released from degenerating tissues of the body (Chaudhary et al., 2001). When the set point of the hypothalamic thermostat becomes increased to higher level than normal, all the mechanisms for raising body temperature are brought into play, inducing heat conservation and increased heat production (Sharma et al., 2006). Fever induced by endotoxin has been used as an experimental tool to study the influence of fever on pharmacokinetics of in different subjects (Ahmad and Nawaz, 1995). Acute fever was produced within 30 minutes after injection of bacterial suspension (E. coli) and it persisted during the experiment. This study was designed to reveal