1.
Bioequivalence Study Of Montelukast Tablets In Healthy Volunteets
by Sadia Amin | Dr. Sualeha Riffat | Prof. Dr. Muhammad Ashraf.
Material type: ; Format:
print
; Nature of contents: ; Literary form: Publisher: 2011Dissertation note: Objective of this bioequivalence study was to compare pharmacokinetic parameters
and to evaluate bioequivalence of two generic drug products. A multinational
company brand was compared with locally manufacture brand. It was a randomized,
single dose, two-period crossover study in which 12 volunteers were participated with
the age limit of 18-30yrs. These volunteers were selected according to different
inclusion and exclusion criteria and the study was conducted with one week washout
period. Each volunteer was one tablet of montelukast (reference or test) lOmg. 14
blood samples of 4-Sml collected at predefined time intervals i.e, 0, O.S, 1.0, 1.S, 2.0,
2.5, 3.0, 3.S, 4.0, 6.0, 8.0, 10, 12 and 24 hours .. Heparinized vacuette were used for
collection of blood samples. After sampling, blood samples were centrifuged
immediately to separate plasma and stored at -80°C till analyzed. Plasma montelukast
concentration was evaluated by using reverse phase - high performance liquid
chromatography (RP-HPLC) method. Potassium dihydrogen phosphate O.OSM at pH
3.5 with orthophosphoric acid in combination to acetonitrile (20:80) was used as
mobile phase. The wavelength of detector was set at 34Snm and flow rate was set to
2.0ml per min. Drug from plasma was extracted by de-proteinizing the plasma with
acetonitrile. 70 III injection volume was given to HPLC for analysis. For comparing
the pharmacokinetic parameters two compartment analysis was used and pair t-test was applied. Non compartmental analysis was used for evaluating pharmacokinetic
parameters to evaluate the both drugs were bioequivalent or not. 3 major parameters
of bioequivalence Cmax, AVC O-inf and AVC O-t were evaluated and they did not
show significant difference in between two formulations. Also the 90% confidence
interval values were within the limit. So, it was concluded that both the test and
reference drug were bioequivalent and test drug could be used interchangeably with
the reference drug.
Availability: Items available for loan: UVAS Library [Call number: 1311,T] (1).
2.
Bioequivalence Study Of Deferiprone In Healthy Volunteers
by Naila Waheed | Dr. Sualeha Riffat | Prof. Dr. Muhammad Ashraf.
Material type: ; Format:
print
; Literary form:
not fiction
Publisher: 2011Dissertation note: The study was conducted with the aim of evaluating bioequivalence, relative
silability and efficacy of deferiprone manufactured locally (Ferinil, Global
aceutical, Pakistan) with a reference drug (Ferriprox, ApoPharma, Canada) in healthy
volunteers. It was a randomized crossover study enrolling 12 volunteers within age limit
g·55yrs and meeting the inclusion and exclusion criteria of the study, Each volunteer was
administered two tablets of deferiprone 500mg of both reference and test drug with a two-
washout period. Blood samples of about 5ml was collected at 0, 0.25, 0.5, 0.75, 1, 1.5, 5,4, 6, 8, 12 hour at predetermined time intervals and one sample was taken as control
giving first dose to volunteers. Heparinized vacuette was used for collection of blood
les. After sampling, blood samples was centrifuged at approximately 3000 rpm for 10
les and then stored at -80°C till analyzed. Plasma deferiprone levels were analyzed using
led High pressure liquid chromatography (HPLC) method. Pharmacokinetic parameters
calculated from plasma concentration time curve non-compartmentally and two-
artmental. After logarithmic transformation of data statistical comparisons of Cmax,
(0-1), AUC(o.oo) was calculated and appropriate statistical method was used for calculation. mean relative bioavailability was 104% and was proved to be bioavailable. The Cmax
(mean ±SD) for reference and test drug was 12.68 ± 4.91 and 14.41 ± 5.04 ug/ml,
ctively while average ± SD of AUCO-t and AUCO-inf of test and reference drug was 40.49
6,05 and 42.84 ± 18.47 ugh/ml and 38.63 ± 13.65 and 40.75 ± 14.17 ugh/ml. Average
(test/reference) of Cmax 90% CI was 0.9876-1.3125. Average ratio (test/reference) of
Co.190% CI was 0.9737-1.1150, and of AUCo-inf 90% CI was 0.9542-1.1343. Therefore both test and reference drug was fairly tolerated by volunteers and no adverse event was
detected. Hence, the average ratio of 90% confidence interval of AUCo-t and AUCO-inf was
0.9737-1.1150 and 0.9542-1.1343 that lie within the acceptable limit of (0.80 - 1.25) for
bioequivalence acceptance. Effectiveness of deferiprone depends on AUC instead of Cmax therefore the average ratio of 90% confidence interval of Cmax was 0.9876-1.3125 that lie
with the acceptable limit of WHO bioequivalence acceptance (0.75 - 1.33). ANOVA show
no significant variations among drug, period and sequence effect. Therefore, it was concluded
that Ferriprox was proved to be bioequivalent in healthy male Pakistani volunleers.
Availability: Items available for loan: UVAS Library [Call number: 1327,T] (1).
