BIOAVAILABILITY OF GLICLAZIDE* PROLONGED RELEASE TABLETS, 30 MG RVG 34591 INTRODUCTION
Gliclazide is a hypoglycaemic sulphonylurea derivative which is indicated for type 2 diabetes
mellitus uncontrolled by diet, exercise and weight loss. It can be used as monotherapy or in
combination with for example metformin and insulin.
Gliclazide, similar as other sulfonylurea derivatives, stimulates insulin secretion from the
pancreatic ß-cells by closing ATP-sensitive potassium channels. Insulin sensitivity also
Gliclazide is progressively released from the tablets upon contact with gastrointestinal fluid.
Gliclazide prolonged release tablets show predictable and reproducible release of gliclazide
over a 24-hour period which parallels the 24-hour glycaemic profile observed in untreated
patients with diabetes mellitus type 2. Plasma concentrations reach a plateau at 3 to 12 hours
after dose. The mean absolute bioavailability of gliclazide is 97%. Gliclazide is highly bound
to albumin (95%). It is extensively metabolized to at least seven metabolites. The plasma
elimination half life is about 16 hours.
Three bioequivalence studies with healthy volunteers, one study in fasting conditions (study
1), one in post-prandial conditions (study 2) and a study comparing steady state conditions
(study 3), were performed to confirm bioequivalence between the test (Gliclazide 30 PCH)
and the reference product (Diamicron UNO 30 mg, Servier GmbH).
* Based on a registration study approved by CBG-MEB
STUDY 1 BIOEQUIVALENCE STUDY WITH GLICLAZIDE UNDER FASTING CONDITIONS EXPERIMENTAL PART
This study was conducted in compliance with Good Clinical Practice (GCP).
Thirty-six healthy volunteers participated in this study and thirty-six subjects completed the
study. The study was designed as a two period, cross-over, controlled, block randomized,
single-dose bioequivalence study. A fasting period of at least 10 hours was established. The
study consisted of two treatment periods separated by a wash-out period of 14 days. In each
treatment period each healthy subject received a single dose (1 x 30 mg) of the test or
reference product in accordance with the randomization scheme. Blood samples were
collected before dosing and at 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0, 11.0, 12.0, 16.0,
20.0 and 24.0, 36.0, 48.0, 60.0, 72.0, 96.0 and 120.0 hours post dosing in each of the two
periods. Plasma samples from all thirty-six subjects were analyzed.
MEASUREMENTS
The concentration of gliclazide was analyzed in the collected blood samples and the following
pharmacokinetic parameters were determined: AUC0-t ; AUC0-∞ ; Cmax
secondary; AUC%extra; T½; MRT as additional parameters. The 90% confidence intervals were
constructed for test/reference ratios of the means of the pharmacokinetic parameters AUC0-t,
AUC0-∞ , Cmax. Bioequivalence was concluded if these confidence intervals fell within the
Thirty-six volunteers completed the study. The pharmacokinetic parameters are reflected in
Table 1. The mean plasma concentrations of gliclazide measured after administration of the
test product and reference product are reflected in Figure 1.
The 90% confidence intervals of the mean ratio (test/reference) were within the acceptance
No serious adverse events were observed during the conduct of this study.
Table 1: Primary pharmacokinetic parameters of test and reference product Parameter Geometric means 90% Confidence geometric Interval Reference AUC0-t (ng/ml * h) AUC0-∞ (ng/ml * h) Cmax (ng/ml) Figure 1:Mean plasma concentration – time profile of gliclazide after oral administration of
30 mg test and reference product, log scale.
STUDY 2 BIOEQUIVALENCE STUDY WITH GLICLAZIDE UNDER FED CONDITIONS EXPERIMENTAL PART
This study was conducted in compliance with Good Clinical Practice (GCP).
Thirty-six healthy volunteers participated in this study and thirty-five subjects completed the
study. The study was designed as a two period, cross-over, controlled, block randomized,
single-dose bioequivalence study. The study consisted of two treatment periods separated by a
wash-out period of 18 days. In each treatment period each healthy subject received a single
dose (1 x 30 mg) of the test or reference product after a high-fat breakfast in accordance with
the randomization scheme. Blood samples were collected before dosing and at 1.0, 2.0, 3.0,
4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0, 11.0, 12.0, 16.0, 20.0, 24.0, 36.0, 48.0, 60.0, 72.0, 96.0 and
120.0 hours post dosing in each of the two periods. Plasma samples from thirty-five subjects
MEASUREMENTS
The concentration of gliclazide was analyzed in the collected blood samples and the following
primary pharmacokinetic parameters were determined to assess bioequivalence: AUC0-t ;
AUC0-∞ ; Cmax as primary; Tmax as secondary; AUC%extra; T½; MRT as additional parameters.
The 90% confidence intervals were constructed for test/reference ratios of the means of the
pharmacokinetic parameters AUC0-t, AUC0-∞ , Cmax. Bioequivalence was concluded if these
confidence intervals fell within the range of 80-125%.
Thirty-five volunteers completed the study. The pharmacokinetic parameters are reflected in
Table 2. The mean plasma concentrations of gliclazide measured after administration of the
test product and reference product are reflected in Figure 2.
The 90% confidence intervals of the mean ratio (test/reference) were within the acceptance
No serious adverse events were observed during the conduct of this study.
Table 2: Primary pharmacokinetic parameters of test and reference product Parameter Geometric means 90% Confidence geometric Interval Reference AUC0-t (ng/ml * h) AUC0-∞ (ng/ml * h) Cmax (ng/ml) Figure 2:Mean plasma concentration – time profile of gliclazide after oral administration of
30 mg test and reference product under fed conditions, log scale.
STUDY 3 BIOEQUIVALENCE STUDY AT STEADY STATE WITH GLICLAZIDE EXPERIMENTAL PART
This study was conducted in compliance with Good Clinical Practice (GCP).
Thirty-six healthy volunteers participated in this study and thirty-six subjects completed the
study. The study was designed as a two period, cross-over, controlled, block randomized,
multiple dose (at steady state) bioequivalence study. The study consisted of two treatment
periods separated by a wash-out period of 16 days. In each treatment period each healthy
subject received a dose (1 x 30 mg) of the test or reference product for six consecutive days in
accordance with the randomization scheme. Blood samples were collected before dosing for
days 1-6 and at 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 8.0, 9.0, 10.0, 11.0, 12.0, 14.0, 16.0, 20.0 and
24.0 hours post dosing for day 6 in each of the two periods. Plasma samples from thirty-six
MEASUREMENTS
The concentration of gliclazide was analyzed in the collected blood samples and the following
pharmacokinetic parameters were determined: AUCss; Cmaxss as primary; Tmax as secondary;
Cminss; %ptf; %Swing; Caverage as additional parameters. The 90% confidence intervals were
constructed for test/reference ratios of the means of the pharmacokinetic parameters AUCss
and Cmaxss. Bioequivalence was concluded if these confidence intervals fell within the range
Thirty-six volunteers completed the study. The pharmacokinetic parameters are reflected in
Table 3. The mean plasma concentrations of gliclazide measured after administration of the
test product and reference product are reflected in Figure 3.
The 90% confidence intervals of the mean ratio (test/reference) were within the acceptance
No serious adverse events were observed during the conduct of this study.
Table 3: Primary pharmacokinetic parameters of test and reference product Parameter Geometric means 90% Confidence geometric Interval Reference AUCss (ng/ml * h) Cmaxss (ng/ml) Figure 3:Mean plasma concentration – time profile of gliclazide after oral administration of
30 mg test and reference product at steady state, log scale.
CONCLUSION
Both formulations were well tolerated, with no major side effects and no relevant differences in
The time concentration profile of Gliclazide 30 PCH was very similar to that of reference
product. Using the evaluation criteria described previously, the parameters Cmax, AUC0-t and
AUC0-∞ and AUCss and Cmaxss fulfil the requirements for bioequivalence.
It can be concluded that Gliclazide 30 PCH is bioequivalent to the reference product under
fasting and fed conditions, in terms of both extent and rate of absorption and at steady state.
P E R S P E C T I VA S F U T U R A S E N E L TA B A Q U I S M O Acomplia. Un nuevo tratamiento para dejar de fumar Unidad Especializada en Tabaquismo, Dirección General de Salud Pública, Comunidad de Madrid El sistema endocannabinoide (SEC) es un sistema fisiológi-El ensayo clínico STRATUS-US es el primero de los tres es-co constituido por un grupo de lípidos endógenos que derivan del
Herbal, Pharmaceutical and Real Medicine Sidney Kurn MD Farmacopia, Santa Rosa, California December, 2011 Herbal, Pharmaceutical and Real Medicine This article is dedicated to the art of medicine and to those who benefit from its “Therapeutics is the noblest pearl and the supreme treasure, and it holds first place in medicine; and there is nothing on earth that can be val
BIOAVAILABILITY OF GLICLAZIDE* 
STUDY 1 BIOEQUIVALENCE STUDY WITH GLICLAZIDE UNDER FASTING 
Table 1: Primary pharmacokinetic parameters of test and reference product 
STUDY 2 BIOEQUIVALENCE STUDY WITH GLICLAZIDE UNDER FED 
Table 2: Primary pharmacokinetic parameters of test and reference product 
STUDY 3 BIOEQUIVALENCE STUDY AT STEADY STATE WITH GLICLAZIDE 
Table 3: Primary pharmacokinetic parameters of test and reference product 
CONCLUSION