Study of the pharmacokinetic changes of Tramadol in diabetic rats

BackgroundBesides the pathological states, diabetes mellitus may also alter the hepatic biotransformation of pharmaceutical agents. It is advantageous to understand the effect of diabetes on the pharmacokinetic of drugs. The objective of this study was to define the pharmacokinetic changes of tramadol and its main metabolites after in vivo intraperitoneal administration and ex vivo perfused liver study in diabetic rat model.Tramadol (10 mg/kg) was administered to rats (diabetic and control groups of six) intraperitoneally and blood samples were collected at different time points up to 300 min. In a parallel study, isolated liver perfusion was done (in diabetic and control rats) by Krebs-Henseleit buffer (containing 500 ng/ml tramadol). Perfusate samples were collected at 10 min intervals up to 180 min. Concentration of tramadol and its metabolites were determined by HPLC.ResultsTramadol reached higher concentrations after i.p. injection in diabetics (Cmax of 1607.5 ± 335.9 ng/ml) compared with control group (Cmax of 561.6 ± 111.4). M1 plasma concentrations were also higher in diabetic rats compared with control group. M2 showed also higher concentrations in diabetic rats. Comparing the concentration levels of M1 in diabetic and control perfused livers, showed that in contrast to intact animals, the metabolic ratios of M1 and M5 (M/T) were significantly higher in diabetic perfused liver compared to those of control group.ConclusionsThe pharmacokinetic of tramadol and its three metabolites are influenced by diabetes. As far as M1 is produced by Cyp2D6, its higher concentration in diabetic rats could be a result of induction in Cyp2D6 activity, while higher concentrations of tramadol can be explained by lower volume of distribution.

• Publication year

  2013

• Venue

  DARU Journal of Pharmaceutical Sciences

• Publication date

  2013-03-07

• Fields of study

  Medicine

• Identifiers
  DOI 10.1186/2008-2231-21-17PMID 23497674PMCID 3610115
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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