ABSTRACT
Drug-drug interactions are most commonly occurring phenomenon in clinical practice. Many physicians are afraid of being involved in an allegation of malpractices due to the occurrence of any severe interaction. These interactions not only occur between drugs but also between any kind of food, tobacco smoke, caffeine and alcohol etc. Therefore, the present study was directed to inspect the effect of caffeine on the anticoagulation activity of warfarin in healthy adult male albino rabbits. Blank blood samples were collected from each rabbit. Rabbits were given warfarin [0.5mg kg-1] orally via stomach tube and blood samples were collected in PT/INR vials at various intervals. After a washout period of 14 days, warfarin was orally administrated at same dose rate along with caffeine [5 mg kg-1 every twelve hours for three days] and same sampling schedule was repeated. Prothrombin time [PT] and the international normalized ratio [INR] of blood samples were determined to estimate changes in the anticoagulation activity of warfarin after its concurrent administration with caffeine. The PT data revealed that Rmax and AUC increased significantly [P=0.05] from 1991.6 and 60.5 to 2124.8 and 67.5, respectively, before and after co-administration. Similarly, a significant [P=0.05] increase was observed in Rmax and AUC of INR from 6.42 and 153.7 to 7.4 and 167.5, respectively, alone and along with caffeine. However, no change was observed in Tmax associated with PT and INR either the drug was administered alone or in combination with caffeine. It was concluded that caffeine has the capacity to inhibit the metabolism of warfarin and enhance its plasma concentration and hence anticoagulant effects. Thus, patients should be advised to limit the frequent use of caffeine-rich products i.e. tea and coffee during warfarin therapy
ABSTRACT
Aim of present study was to investigate the pharmacokinetic behavior of Montelukast in the healthy male volunteers under indigenous conditions. One tablet of montelukast 10 mg was administered in each subject and blood at different time intervals. Concentration of montelukast in plasma samples was analyzed by high performance liquid chromatography method to calculate pharmacokinetic parameters. The plasma concentration of montelukast was in the range of 1.31-1.76 micro g/mL at 0.5-12 hours with C[max] value of 1.59+/-0.16 micro g/mL at 3.71+/-0.64 hours. These values of plasma drug concentrations were above the minimum effective concentration of montelukast during the entire study hours. Absorption and elimination half-lives of the montelukast were evaluated as 2.52+/-0.54 hours and 2.63+/-0.35 hours, respectively. The volume of distribution and total body clearance of montelukast were investigated as 0.34+/-0.01 L/kg and 0.01+/-0.00 L/hr/kg, respectively. The pharmacokinetic parameters i.e. Cmax, AUC, t1/2, Vd and ClB of montelukast calculated in present study were found different as compared to that of the previous literature values which was due to genetic and environmental variation