Abstract
The present study was aimed to evaluate the clarithromycin pharmacokinetics after atorvastatin single and repeated dose administration in induced hyperlipidemic Wistar rats. A high fat diet (2% cholesterol) was used to induce hyperlipidemia and feed was given to rats for 6 to 8 weeks. Group allocation was as follows: G1 to G3: induced hyperlipidemic rats pretreatment of atorvastatin as a single dose followed by clarithromycin single doses of 10, 20 and 100 mg/kg; G4 to G6: induced hyperlipidemic rats pretreatment of atorvastatin for 7 consecutive days followed by clarithromycin single doses of 10, 20 and 100 mg/kg; G7 to G8: atorvastatin treated hyperlipidemia rat livers harvested on day 1 and 7 post dose; G9 to G10: concomitant administration of atorvastatin and clarithromycin in presence and absence of hyperlipidemia for biliary and urinary excretion studies. Effect of atorvastatin on hyperlipidemia and alterations of clarithromycin kinetics due to various states of hyperlipidemia like induced, reduced and absence of hyperlipidemia was evaluated. The in vitro clarithromycin results suggested down/up regulation of CYP mediated metabolism in induced and reduced hyperlipidemia rats. Clarithromycin pharmacokinetics was considerably affected by hyperlipidemia and also recovered kinetics and metabolism in presence of atorvastatin compared on days 1 and 7 were also reported. The decreased area under the curve of clarithromycin in hyperlipidemic rats after co-administration of atorvastatin might be mainly due to up regulation of the CYP mediated metabolism by reducing the hyperlipidemia in the liver. Key words: Clarithromycin, atorvastatin, hyperlipidemia, area under the curve (AUC), peak plasma, rats.
Highlights
Hyperlipidemia (HL) is defined as an elevation of one or more of the plasma lipids, including cholesterol, cholesteryl esters, triglycerides or phospholipids (Raasch, 1988)
The main objective of this work was to investigate the severity of induced hyperlipidemic rats (IHL) on CLR pharmacokinetics and the severity of IHL was evaluated by AT, following single dose and repeated dose for 7 consecutive days by oral gavage administration, followed by single oral
The corresponding pharmacokinetic parameters are shown in pharmacokinetic parameters were significantly recovered and the same was re-evaluated by administration of AT
Summary
Hyperlipidemia (HL) is defined as an elevation of one or more of the plasma lipids, including cholesterol, cholesteryl esters, triglycerides or phospholipids (Raasch, 1988). Despite the differences in lipoprotein distribution and metabolism between humans and rats, hyperlipidemic (HLM) rat models are used extensively in lipid research. Many hyperlipidemic rat models are in existence (Eliot et al, 1999). Antimicrobial drugs manifest a wide variety of drug interactions which can differ greatly in their extent of severity and clinical relevance. Co-medication and food and herbal medicine can interact with antimicrobial.
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