ABSTRACT
Warfarin is a commonly prescribed anticoagulant existing in two enantiomeric forms S- and R-warfarin. Many techniques have been used to analyze warfarin in plasma but less frequently for enantiomeric analysis. One of the HPLC method employed was further simplified and made economical. Method was validated according to ICH guidelines and was found to be sensitive, reliable and less time consuming. For both enantiomers, LLOQ was 12.5ng/mL. The CV% and accuracy for method were in the range of 0.8-14.6% and 92-107% respectively. The recoveries for both enantiomers were in the range of 86-103.8%. Blood samples were collected from 170 stable patients taking warfarin and S- and R-warfarin levels were determined by this method. Majority of subjects were found to have S/R-warfarin ratio of about 1:2 as reported in previous studies due to rapid clearance of S-enantiomer than R-enantiomer. However individual subjects data was suggestive of presence of slow metabolizers of S-warfarin leading to altered S/R ratio. Previous studies have also pointed out CYP2C9 polymorphism being responsible for such inter-individual differences in S-warfarin metabolism. So plasma warfarin S/R ratio may serve as a useful phenotypic test for CYP2C9 polymorphism
ABSTRACT
Carvedilol is an anti-hypertensive agent capable of blocking both alph [a] and beta [p] receptors used to preclude cardiac arrhythmias and angina
The study was designed to evaluate the Pharmacokinetics of carvedilol in human male and female volunteers
Healthy male and female [twenty each] volunteers were finalized for the study after preliminarily clinical examination. Blood samples were collected at specific time intervals after giving an oral dose of 12.5mg carvedilol, separated the plasma and placed at -80°C until analysis. Estimation of carvedilol in human plasma was accomplished by High performance liquid chromatographic [HPLC] method using fluorescent detector
Plasma concentration-time curve was used for calculation of pharmacokinetic parameters using two-compartment open model
Mean [SD] values of AUC and C[max] 0.076+/-0.021microg.h/ml and 0.024+/-0.005microg/mL, respectively] in male differ significantly [P<0.05] from the female 0.197+/-0.042jug.h/ml and 0.048+/-0.02microg/mL, respectively]
Overall, bioavailability of carvedilol was somewhat higher in females than in males, but these differences could be expounded by the lower body weight of female
Conversely, no significant differences were found for tmax, clearance and half-life in male and female
Moreover the ethnicity had significant impact on the Pharmacokinetics of carvedilol in human
ABSTRACT
Montelukast is a leukotrien receptor antagonist used for asthma treatment. Objective of this study was to evaluate the bioequivalence of two montelukast 10mg tablets, Innovator drug [Singulair] as reference and other locally manufactured drug [Montiget] in 12 healthy volunteers. It was randomized, single dose, two-period crossover study with 1 week washout period. Blood samples [4-5 ml] were collected before and after drug administration and plasma was separated for analysis. Concentrations of montelukast at different time intervals were determined by validated UV-HPLC method at 345nm wavelength. Bioequivalence was assessed by using non compartmental approach and also calculated the 90% confidence interval of the least-squared pharmacokinetic parameters [C[max], AUC[0-t] and AUC[0-infinity]]. On average, C[max], AUC[0-t], AUC[0-inf], was 2.35 micro g/ml, 1.28 micro g.h./ml, 1.67 micro g.h./ml, for innovator drug and 2.53 micro g/ml, 1.53 micro g.h./ml, 1.96 micro g.h./ml, for test drug, respectively. Confidence interval [90%] for C[max], AUC[0-t] and AUC[0-inf] was 89-97%, 85-91% and 81-98% respectively. No statistical difference was found between the C[max] and AUC values of test and reference drugs. The confidence intervals for C[max], AUC[0-t] and AUC[0-infinity] are fully laid within the acceptable range of FDA [80-125%], thus two formulations are considered to be bioequivalent