Disposition kinetics, renal clearance and urinary excretion of cefixime in adolescent Pakistani boys - DRUG ANALYSIS REPORT.

OBJECTIVE: To investigate the role of environmental variation, genetic differences and age on disposition kinetics, renal clearance and urinary excretion of oral cefixime 400mg in healthy boys. METHODS: The cross-sectional study was conducted at the University of Agriculture, Faisalabad, Pakistan, from August 2014 to July 2015, and comprised healthy boys aged 12-17 years after oral administration of cefixime capsule 400mg. Serum and urine samples were collected before and after drug administration and were stored at - 20oC until evaluation of cefixime concentration in each sample by high performance liquid chromatography. Drug concentration versus time data was used for pharmacokinetic calculations using one compartment model. Data obtained for urinary excretion and renal clearance of cefixime was analysed using regression-correlation analysis. RESULTS: There were eight boys in the study. Mean values for elimination half-life, volume of distribution and total body clearance were 2.4}0.2 hours, 0.9}0.0L/kg and 0.3}0.0L/h/kg, respectively. The ratio of renal clearance of cefixime (0.7 ml/min/kg) to that of endogenous creatinine (0.8ml/min/kg) was 0.9. Cumulative mean percentage of cefixime excreted from young adolescent boys was 11.6 } 0.5%. CONCLUSION: Other than filtration, back-diffusion was also involved in renal handling of cefixime. There was enough indication that major portion of cefixime was excreted from a young body through bile.

Effect of caffeine on anti-clotting activity of warfarin in healthy male albino rabbits.

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.

Pharmacokinetic behavior of montelukast in indigenous healthy male volunteers.

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 1.31-1.76µg/mL at 0.5-12 hours with Cmax value of 1.59±0.16µg/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.