INVIVO EVALUATION OF THE EFFECTS OF Allium sativum ON THE PHARMACOKINETIC PARAMETERS OF CIPROFLOXACIN AND ISONIAZID.

Objective: The pharmacokinetic parameters of isoniazid and ciprofloxacin administered orally to garlic (Allium sativum) pretreated rats of both sex divided into four groups of five rats per group was determined. Methods: Two groups received ciprofloxacin 20 mg/kg and Isoniazid 15 mg/kg respectively while the other groups received garlic extract for 10 days followed by the administration of ciprofloxacin or Isoniazid on the 11th day. Blood samples were collected from each group at different time interval and plasma concentrations of the drugs determined spectrophotometrically. The pharmacokinetic parameters were determined using the non-compartmental method as implemented in win Nonlin. Secondly, the effect of Allium sativum on the lung penetration of the drugs at same dose range was determined also in rats. Results: Garlic significantly increased the AUC of ciprofloxacin from 119.00±0.962 to 256.32±0.680 and decreased Vd from 1.13±0.172 to 0.90±0.009 and CL from 0.16±0.011 to 0.062±0.001. The AUC of INH was also increased from 491.84±56.765 to 574.04±50.600 and CL was significantly decreased from 0.02±0.007 to 0.01±0.003 where as Vd showed little or no change, (0.397±0.009/0.42±0.143). Garlic increased the maximum concentration of ciprofloxacin achieved in the lung fluid and the time to attain this concentration was delayed, while the maximum concentration of INH achieved in the presence and absence of the herb showed no difference though, the time to attain this concentration were delayed. Conclusion: Our findings therefore suggested that the co-administration of garlic with ciprofloxacin or Isoniazid may pose a negative clinical implication of increased drug toxicity and/or adverse effects. Keywordspharmacokinetics, garlic, ciprofloxacin, Isoniazid, interaction, in vivo, lung, penetration. International Journal of Drug Discovery ISSN: 0975-4423 & E-ISSN: 0975-914X, Volume 4, Issue 1, 2012 Introduction The use of herbal supplements as natural remedies is popular these days. Many of these herbal supplements can interact with prescription and non-prescription medications sometimes with severe consequences. For instance, one report found that garlic reduced the plasma saquinavir level [1]. Similarly, an extract of green tea taken by healthy women with a meal inhibited the absorption of non-heme iron (e.g., the form of iron in plant foods) by 26% [2] and consuming large amount of these substances while taking theophylline, increases the risk of drug toxicity. Garlic is a bulb of a lily-like plant belonging to the same family as onions and has been used as herbal remedy for some common ailments. It has been shown to promote wound healing and prevent cold and influenza. Garlic produces significant reduction in total cholesterol and triglyceride [3] and effective in hypertension reduction [4]. Some also have it that garlic may reduce the risk of cancers of the stomach and colon [5]. Several preclinical studies have shown that garlic constituents can modulate the activities of various drug metabolizing enzymes. Fresh garlic extracts and commercially available garlic products were shown to inhibit cytochrome P450 isoforms 2C9*1, 2C19, and 3A4 during metabolism of a marker substrate [6]. Garlic oil and its three allyl sulfide components administered for six weeks have been shown to lead to enhanced activities and increased expression of CYP 3A1, 2B1 and 1A1 in the hepatic detoxification system of rats [7]. In a study in healthy volunteers, a 3-week administration of a garlic supplement decreased plasma concentrations of the protease inhibitor saquinavir by about 50% [1]. Similarly, garlic formulations have been shown to inhibit human CYP3A4 mediated metabolism and P-glycoprotein mediated transport in vitro [7]. Citation: Nduka S.O., Okonta J.M. and Esimone C.O. (2012) Invivo Evaluation of the Effects of Allium sativum on the Pharmacokinetic Parameters of Ciprofloxacin and Isoniazid. International Journal of Drug Discovery, ISSN: 0975-4423 & E-ISSN: 0975-914X, Volume 4, Issue 1,