title: Bioequivalence study of two losartan tablet formulations with special emphasis on cardiac safety.
abstract: OBJECTIVE
  To study the bioequivalence of Losartan Potassium Tablets 50 mg manufactured by Micro Labs Ltd. India to Cozaar® Tablets 50 mg, manufactured by Merck Sharp and Dohme Ltd., UK in normal healthy adult subjects under fasting condition along with the comparative safety evaluation of both treatments.
  
  
  METHODS
  The in vitro dissolution studies were carried out on 12 units each of test and reference products using the paddle method and dissolution media like water, 0.1 N hydrochloric acid with pH 1.2, pH 4.5 acetate buffer and pH 6.8 phosphate buffer. An open label, randomized, two-treatment, two-period, two-sequence, crossover bioequivalence study with a washout period of 7 days was conducted in 60 healthy Indian male subjects. Serial blood samples were collected after drug administration in each study period. Plasma concentrations of losartan and losartan acid were determined using a validated LC-MS-MS method. The pharmacokinetic parameters of losartan and losartan acid were determined using a non compartmental model. Occurrence of adverse events, change in systolic blood pressure, diastolic blood pressure, heart rate and QT interval from the baseline to 3.50 h post dose were studied and compared between the two treatments as safety parameters.
  
  
  RESULTS
  The in vitro study proved the essential similarity of both the formulations as evident from the similarity factor of > 50% in all the dissolution media. The ratios for geometric least square means and 90% confidence intervals were within the acceptance criteria of 80% to 125% for log transformed C(max), AUC(0-t) and AUC(0-∞) for losartan. No statistically significant difference between the two treatments was observed for either of the safety parameters.
  
  
  CONCLUSIONS
  The test product Losartan Potassium tablets 50 mg manufactured by Micro Labs Limited, India was bioequivalent to Cozaar® tablets 50 mg, manufactured by Merck Sharp and Dohme Ltd., UK in terms of rate and extent of absorption. Both treatments were well tolerated and had similar non significant effect on the safety parameters.
authors.affiliation: Accutest Research Laboratories (I) Private Limited, Navi Mumbai, Maharashtra, India. suhas_khandave@rediffmail.com
authors.forename: Suhas S
authors.initials: SS
authors.lastname: Khandave
authors.forename: Satish V
authors.initials: SV
authors.lastname: Sawant
authors.forename: Rakhi V
authors.initials: RV
authors.lastname: Sahane
authors.forename: Vivekanand
authors.initials: V
authors.lastname: Murthi
authors.forename: Shivanand S
authors.initials: SS
authors.lastname: Dhanure
authors.forename: Pradeep G
authors.initials: PG
authors.lastname: Surve
mesh_terms: D000293:Adolescent; D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000493:pharmacokinetics*; D000959:Antihypertensive Agents / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D006321:Heart / Q000187:drug effects*; D006801:Humans; D019808:Losartan / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D012995:Solubility; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D013607:Tablets; D019808:Losartan