title: Herb-drug interaction of Andrographis paniculata (Nees) extract and andrographolide on pharmacokinetic and pharmacodynamic of naproxen in rats.
abstract: BACKGROUND
  Andrographis paniculata Nees (Acanthacae) have broad range of pharmacological effects such as hepatoprotective, antifertility, antimalarial, antidiabetic, suppression of various cancer cells and anti-inflammatory properties and is widely used medicinal plant in the traditional Unani and Ayurvedic medicinal systems. 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 naproxen (NP) after oral co-administration in wistar rats.
  
  
  METHODS
  After oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with NP (7.5mg/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 NP with APE and pure AN decreased systemic exposure level of NP in vivo. The Cmax, tmax,AUC0-tof NP was decreased. In pharmacodynamic study, NP (10mg/kg) alone and NP+AN (10+60mg/kg) groups exhibited significant synergistic anti-arthritic activity as compared to groups NP+APE, APE and AN alone.
  
  
  CONCLUSIONS
  The results obtained from this study suggested that NP, APE and pure AN existed pharmacokinetic herb-drug interactions in rat which is correlated with anti-arthritic study. The knowledge regarding possible herb-drug interaction of NP might be helpful for physicians as well as patients using AP. So further studies should be done to understand the effect of other herbal ingredients of APE on NP as well as to predict the herb-drug interaction in humans.
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 Pharmaceutical Chemistry, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University (BVDU), Pune 411038, India.
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; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001169:Arthritis, Experimental / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D002851:Chromatography, High Pressure Liquid; D004224:Diterpenes / Q000008:administration & dosage* / Q000302:isolation & purification; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D005620:Freund's Adjuvant; D006207:Half-Life; D041743:Herb-Drug Interactions; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D008657:Metabolic Clearance Rate; D009288:Naproxen / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D059225:Nociception / Q000187:drug effects; D059226:Nociceptive Pain / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D017288:Pain Threshold / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage* / Q000302:isolation & purification; D010946:Plants, Medicinal; D017208:Rats, Wistar
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D010936:Plant Extracts; C030419:andrographolide; D009288:Naproxen; D005620:Freund's Adjuvant
keywords: Andrographis paniculata nees extract; Andrographolide; Andrographolide (Pubchem CID: 5318517); Carbamazepine (Pubchem CID: 2554); Herb–drug Interaction; Naproxen; Naproxen (Pubchem CID: 156391); Pharmacodynamic; Pharmacokinetic