Hepatoenteric recycling is a new disposition mechanism for orally administered phenolic drugs and phytochemicals in rats

Many orally administered phenolic drugs undergo enterohepatic recycling (EHR), presumably mediated by the hepatic phase II enzymes. However, the disposition of extrahepatically generated phase II metabolites is unclear. This paper aims to determine the new roles of liver and intestine in the disposition of oral phenolics. Sixteen representative phenolics were tested using direct portal vein infusion and/or intestinal perfusion. The results showed that certain glucuronides were efficiently recycled by liver. OATP1B1/1B3/2B1 were the responsible uptake transporters. Hepatic uptake is the rate-limiting step in hepatic recycling. Our findings showed that the disposition of many oral phenolics is mediated by intestinal glucuronidation and hepatic recycling. A new disposition mechanism ‘Hepatoenteric Recycling (HER)”, where intestine is the metabolic organ and liver is the recycling organ, was revealed. Further investigations focusing on HER should help interpret how intestinal aliments or co-administered drugs that alter gut enzymes (e.g. UGTs) expression/activities will impact the disposition of phenolics.

Determination of Methyldopa and Paracetamol in Pharmaceutical Samples by a Low Cost Genipa americana L. Polyphenol Oxidase Based Biosensor

Purpose: Jenipapo fruit (Genipa americana L) is a natural source of polyphenol oxidases (PPOs) whose potential in pharmaceutical analysis is noteworthy. Henceforth, this work reports the electrochemical study of a low-cost PPO-based biosensor produced from the crude extract of Jenipapo fruits and accounts a practical approach to employ this biosensor in the determination of methyldopa and paracetamol in pharmaceutical samples. Methods: In order to investigate the electrochemical properties of the biosensor, theoretical and practical approaches were employed, and both samples and the biosensor were analyzed through electrochemical impedance spectroscopy (EIS) and voltammetric techniques, namely: differential pulse voltammetry (DPV) and cyclic voltammetry (CV). Results: showcased that the biosensor presented good analytical features, as well as low detection limits (8 μmol L-1 for methyldopa and 5 μmol L-1 for paracetamol). The relative standard deviation was less than 5% mid-assay. Conclusion: The use of this biosensor is a reliable, low cost and useful alternative in the pharmaceutic determination of phenolic drugs (e.g. methyldopa and paracetamol).

Spectrophotometric Method for the Determination of Drugs Containing Phenol Group by Using 2, 4- Dinitrophenylhydrazine

A spectrophotometric method has been proposed for the determination of four phenolic drugs; salbutamol, ritodrine, amoxicillin and isoxsuprine. The method is based on the oxidation of 2, 4- dinitrophenyl-hydrazine and coupling of the oxidized product with drugs to give intensely colored chromogen. Under the proposed optimum condition, beer’s law was obeyed in the concentration range of 2.5-17, 2-29, 4-33 and 5-30 μg/mL for salbutamol, ritodrine, amoxicillin and isoxsuprine respectively. The limit of detection (LOD) and limit of quantification (LOQ) were 0.2, 0.83, 0.09, 0.84 μg/mL and 0.66, 2.79, 0.3 and 2.81 μg/mL in the same order. No interference was observed from common pharmaceutical adjuvants. The ringbom plots and low relative standard deviation assert the applicability of this method. The suggested method was further applied for the determinations of drugs in commercial pharmaceutical dosage forms, which was compared statistically with reference methods by means oft- test andF- test and were found not to differ significantly at 95% confidence level. The procedure is characterized by its simplicity with accuracy and precision.