title: Pharmacokinetic and pharmacodynamic herb-drug interaction of Andrographis paniculata (Nees) extract and andrographolide with etoricoxib after oral administration in rats.
abstract: BACKGROUND
  Andrographis paniculata Nees (Acanthacae) is commonly used medicinal plant in the traditional. Unani and Ayurvedic medicinal systems. It has broad range of pharmacological effects such as hepatoprotective, antioxidant, antivenom, antifertility, inhibition of replication of the HIV virus, antimalarial, antifungal, antibacterial, antidiabetic, suppression of various cancer cells and anti-inflammatory properties. Andrographolide (AN) is one of the active constituent of the A. paniculata Nees extract (APE). They have been found in many traditional herbal formulations in India and proven to be effective as anti-inflammatory drug
  
  
  OBJECTIVE
  To evaluate the pharmacokinetic and pharmacodynamic (anti-arthritic) herb-drug interactions of A. paniculata Nees extract (APE) and pure andrographolide (AN) with etoricoxib (ETO) after oral co-administration in wistar rats.
  
  
  METHODS
  After oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with ETO (10mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of Cmax, tmax, t1/2, MRT, Vd, CL, and AUC were calculated by non-compartment model. Change in paw volume, mechanical nociceptive threshold, mechanical hyperalgesia, histopathology and hematological parameters were evaluated to study antiarthritic activity.
  
  
  RESULTS
  Co-administration of ETO with APE and pure AN decreased systemic exposure level of each compound in vivo. The Cmax, AUC, t1/2 of ETO was decreased whereas Vd and CL of ETO was increased significantly after co-administration of ETO with pure AN and APE. In pharmacodynamic study, ETO alone and ETO+APE (10+200mg/kg) groups exhibited significant synergistic anti-arthritic activity as compared to groups ETO+AN, APE and AN alone.
  
  
  CONCLUSIONS
  The results obtained from this study suggested that ETO, APE and pure AN existed pharmacokinetic herb-drug interactions in rat which is correlated with anti-arthritic study. Physicians and patients using A. paniculata should have the knowledge about its possible herb-drug interaction with ETO.
authors.affiliation: Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University (BVDU), Pune 411038, India.
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Balap
authors.affiliation: Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University (BVDU), Pune 411038, India.
authors.forename: Bhagyashri
authors.initials: B
authors.lastname: Atre
authors.affiliation: Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University (BVDU), Pune 411038, India. Electronic address: pharmsathiya@gmail.com.
authors.forename: Sathiyanarayanan
authors.initials: S
authors.lastname: Lohidasan
authors.affiliation: Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University (BVDU), Pune 411038, India.
authors.forename: Arulmozhi
authors.initials: A
authors.lastname: Sinnathambi
authors.affiliation: Department of Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University (BVDU), Pune 411038, India. Electronic address: krmahadik@redifffmail.com.
authors.forename: Kakasaheb
authors.initials: K
authors.lastname: Mahadik
mesh_terms: D000284:Administration, Oral; D035685:Andrographis / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D000975:Antioxidants / Q000493:pharmacokinetics / Q000494:pharmacology; D001168:Arthritis / Q000188:drug therapy / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004224:Diterpenes / Q000493:pharmacokinetics* / Q000494:pharmacology; D000077613:Etoricoxib; D005260:Female; D041743:Herb-Drug Interactions; D010936:Plant Extracts / Q000493:pharmacokinetics* / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry; D011725:Pyridines / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013450:Sulfones / Q000493:pharmacokinetics* / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004224:Diterpenes; D010936:Plant Extracts; D011725:Pyridines; D013450:Sulfones; C030419:andrographolide; D000077613:Etoricoxib
keywords: Andrographis paniculata extract; Andrographolide; Andrographolide (Pubchem CID: 5318517); Celecoxib (Pubchem CID: 2662); Etoricoxib; Etoricoxib (Pubchem CID: 123619); Herb–drug Interaction; Pharmacodynamics; Pharmacokinetics