Original Article 177

A Comparative Pharmacokinetic Study of a Fixed Dose

Combination for Essential Hypertensive Patients:
A Randomized Crossover Study in Healthy Human
Volunteers

Authors B. Gorain1, H. Choudhury1, D. Halder1, A. K. Sarkar1, P. Sarkar1, E. Biswas1, B. Ghosh2, T. K. Pal1

1
Affiliations Department of Pharmaceutical Technology, Bioequivalence Study Centre, Jadavpur University, Kolkata, India
2
Department of Pharmacology, Kolkata Medical College and Hospital, Kolkata, India

Key words Abstract

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Results: Test and reference formulations
●
▶ hypertension

●
▶ bioavailability
▼ gave a mean Cmax of 5.234 ± 0.914 ng/mL and
Background: This study was aimed to investi- 4.991 ± 0.563 ng/mL, 108.839 ± 13.601 ng/mL and
●
▶ amlodipine

●
▶ telmisartan
●
▶ hydrochlorothiazide
●
▶ pharmacokinetics
received 10.12.2012
accepted 28.01.2013
Bibliography
DOI http://dx.doi.org/
10.1055/s-0033-1334882
Published online:
March 7, 2013
Drug Res 2013;
63: 177–184
© Georg Thieme Verlag KG
Stuttgart · New York
ISSN 2194-9379
Correspondence
Prof. (Dr.) T. K. Pal
Department of Pharmaceutical
Technology
Bioequivalence Study Centre
Jadavpur University
Raja S. C. Mullick Road
Kolkata-700 032
India
Tel.: + 91/33/2414 6967
Fax: + 91/33/2414 6186
proftkpal@gmail.com
gate the relative bioavailability of fixed-dose-
combination (FDC) product of amlodipine,
telmisartan and hydrochlorothiazide with indi-
vidual marketed products in healthy male volun-
teers. Control of blood pressure with fixed dose
combination of the above drugs acting through
different mechanism have a benefit of conven-
ient dosing in terms of compliance, lower the
dose and subsequently reduce the side effects.
Methods: The authors investigated the relative
bioavailability under a fasting state of the 3
drugs in a randomized, open-label, 2-treatment,
2-period, 2-sequence, crossover bioequivalence
study with a washout period of 21 days. Plasma
concentration of the analytes were assayed in
timed samples with a simple, highly sensitive
and rapid validated method using HPLC coupled
to tandem mass spectrometry that had a lower
limit of quantification of 1 ng/mL for all the 3
components.
Background
▼ tensive agents from different pharmacologic
Cardiovascular diseases (CVD) are the leading
causes of death among adults in the industrial-
ized world as well as in developing countries, and
will probably remain so in the near future.
Hypertension is one of the most prevalent risk
factors for the development of cardiovascular
complications such as left ventricular hypertro-
phy, myocardial infarction, stroke, and renal dis-
eases. By 2020, CVD will be the largest cause of
deaths in India [1]. However, if blood pressure
(BP) is effectively controlled, target-organ dam-
age can be prevented and, in the long term, the
likelihood of these complications can be reduced
[2, 3].
114.783 ± 12.315 ng/mL and 97.814 ± 10.779 ng/
mL and 93.731 ± 10.018 ng/mL for amlodipine,
telmisartan and hydrochlorothiazide respec-
tively. The AUC0-t of amlodipine, telmisartan
and hydrochlorothiazide was 161.484 ng.h/mL,
1 917.644 ng.h/mL and 822.847 ng.h/mL for test
formulation and 162.108 ng.h/mL, 2 014.764 ng.h/
mL and 829.323 ng.h/mL for reference in the fast-
ing state.
Conclusion: The 90 % confidence intervals for
the test/reference ratio of the pharmacokinetic
parameters in fasting state (mean Cmax, AUC0-t,
and AUC0-∞) were within the acceptable range of
80.00–125.00. Thus, these findings clearly indi-
cate that the FDC product is bioequivalent with
the individual marketed products in terms of rate
and extent of drug absorption and is well toler-
ated with no significant adverse reactions.
The rationale for combining 2 or more antihyper-
classes is based on the expectation that the com-
bination will exert an additive or synergistic
antihypertensive effect when compared to single
drug treatment to non-responders/in case of
essential hypertensive patients. Treatment of
essential hypertension, where blood pressure
control is difficult, is targeted from single drug
therapy to multi drug combinations of drugs
exhibiting different mechanisms of action. As
multiple factors involved in generation of hyper-
tension, the combination of different drugs act-
ing through different mechanisms will effectively
control this risky disease. The prime objective for
such therapy is the synergistic response at low
dose level of individual components in order to

Gorain B et al. A Randomized, Crossover Bioequivalence Study … Drug Res 2013; 63: 177–184
178 Original Article
control of BP [4], thereby reduces mortality and morbidity asso-
ciated with stroke and coronary heart disease [4] and the
reduced dose in combination therapy may even counteract side-
effects of each other [5, 6]. Treatment with individual drug in such
condition is unrealistic approach. In addition, combining 2 or more
agents may improve patient compliance and enhance tolerability
by reducing the incidence of certain side effects that are more
prevalent when the drugs are used alone. The seventh report of
the Joint National Committee on Prevention, Detection, Evalua-
tion, and Treatment of High Blood Pressure (2004) has emphasized
the importance of achieving blood pressure goals through aggres-
sive treatment with multiple medications, if needed [7].
Many clinical trials with combinations have been tried and few
are available worldwide. Angiotensin receptor blockers (ARBs)
were evaluated in combination with either hydrochlorothiazide
or calcium channel blockers (CCBs) for their use in essential
hypertension. Recent research evidences showed superior effi-
cacy of such combinations over monotherapies, with modest
adverse events [8, 9]. ARB combination with thiazide diuretics
like hydrochlorothiazide is getting increasingly popular in the
antihypertensive therapy and prescriptions are continuing to be
switched to these combinations [10]. The likelihood of develop-
ment of pedal edema with CCB like amlodipine is decreased
when combined with an ARB [11]. Recently, more than 2 drugs
are combined for better clinical outcomes in essential hyperten-
sion. ARB-CCB-thiazide diuretics like hydrochlorothiazide fixed
dose combinations were also developed on the same lines [4].
Randomized clinical trials were tested for efficacy & safety for
ARB-CCB-thiazide diuretic like hydrochlorothiazide and it has
been confirmed that triple combination is superior in BP reduc-
tion, compared to monotherapy/dual combinations and it also
showed comparable tolerability [12, 13].
The major advantage with fixed-dose combinations of CCBs like
amlodipine (CAS No. 88150-42-9; ● ▶ Fig. 1a) with ARB like tel-
misartan (144701-48-4; ● ▶ Fig. 1b) and thiazide diuretic hydro-
chlorothiazide (CAS No. 58-93-5; ● ▶ Fig. 1c) is that more patients
achieve BP normalization more quickly with initial therapy.
Amlodipine decreases arterial smooth muscle contractility and
subsequent vasoconstriction by blocking the calcium channel,
hydrochlorothiazide inhibits water reabsorption in the nephron
by inhibiting the sodium-chloride symporter in the distal convo-
luted tubule and telmisartan is a selective AT1 subtype angi-
otensin II receptor antagonist, thereby decreasing the blood
pressure. Changes in regimens to optimize control contribute to
treatment “turbulence” that is associated with the loss of patient
confidence and compliance problems. Therefore, for the first
time we investigated the relative bioavailability of the fixed dose
combination of amlodipine, telmisartan and hydrochlorothi-
azide tablet with the separately available marketed products of
those drugs in a crossover clinical trial under the fasting state in
Gorain B et al. A Randomized, Crossover Bioequivalence Study … Drug Res 2013; 63: 177–184
Fig. 1 Chemical structures of Amlodipine a
Telmisartan b and Hydrochlorothiazide c.
24 healthy male human volunteers. We also determined the
bioequivalence of different formulations.
Methods
▼
Test and reference medications
Test preparation of FDC tablet
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Test preparation of F.D.C. tablet (containing amlodipine 10 mg,
telmisartan 80 mg and hydrochlorothiazide 25 mg) gifted by
Akums Drugs & Pharmaceuticals Ltd., Delhi, India.
Reference preparations
Tablet Amlogard-10 (containing amlodipine 10 mg) manufactured
by Pfizer Pharmaceutical India Pvt. Ltd., India (Batch No. 120-
05101), tablet Telday (containing telmisartan 80 mg) manufac-
tured by Torrent Pharmaceutical Ltd, India (Batch No. CC121003)
and tablet Aquazide (containing hydrochlorothiazide 25 mg) man-
ufactured by Sun Pharmaceuticals Industries Ltd., India (Batch No.
BSK0360) were purchased from local pharmacy stores.
Study subjects
The study has been conducted in accordance with the relevant
articles of the Declaration of Helsinki (1964) and its latest revi-
sions (2008) [14]; amended version of Schedule Y [2005] CDSCO,
India [15]; as well as the ethical norms laid down by the Indian
Council of Medical Research (ICMR), New Delhi, India, 2006 [16];
protocol and SOPs of Bioequivalence Study Centre.
Before being enrolled in the clinical study, each volunteer signed
a written informed consent after being informed about the
nature, scope, possible consequences and design of the study.
Before the start of the study, all documents were reviewed and
approved by Drugs Control General of India (DCGI) and Institu-
tional Ethical Committee of Jadavpur University prior to the
start of the study.
On the basis of laboratory tests (hematology, biochemistry and
serology), medical history, physical examination and on fulfill-
ment of following inclusion criteria: male, aged between 18 and
45 years, physically and mentally healthy as judged by standard
physical and laboratory examinations, normal ECG, normal
blood pressure and heart rate and body mass index (BMI)
between 18 and 25 kg/m2 and willingness to provide written
informed consent, a total of 24 volunteers (age, 24.29 ± 2.85
years; weight, 65.17 ± 4.18 kg; height, 169.25 ± 4.18 cm; BMI,
22.72 ± 0.76 kg/m2 [mean ± standard deviation]) included in the
trial according to the protocol. No alcohol or concomitant medi-
cation was allowed 72 h prior to the initial administration of the
dose and for the entire duration of the study. All subjects
reported to the study site at least 12 h prior to the administra-
tion of the study drug. None of the subjects had a previous his-

tory of allergy to ARB agents, CCBs and thiazide diuretic or any
excipient thereof.
Study design and procedures
This was a randomized, open-label, 2 treatment, 2 period, 2
sequence, crossover comparative oral bioavailability study. All
the subjects arrived at the study center at least 13 h prior to the
start of the study. They were housed in an closed facility at Clin-
ical Pharmacology Unit and were given a standard dinner, which
was finished at least 10 h before dosing in each period of the
study. In periods I and II, participants received a single dose of
either test product (FDC tablet containing amlodipine 10 mg, tel-
misartan 80 mg and hydrochlorothiazide 25 mg) or reference
product (separate marketed products of the above) as per rand-
omization schedule with 240 ± 2 mL of plain drinking water at a
gap of 21-day washout (t1/2 = 30–50 h, 24 h, and 6–15 h for
amlodipine, telmisartan and hydrochlorothiazide respectively)
[17] between the 2 periods (● ▶ Fig. 2). The intake of the study
formulations was closely monitored by a physician and the oral
cavity was checked properly to ensure completion of the admin-
istration process. All the subjects were in sitting posture or
ambulatory for first 2 h after dosing. Drinking water was restricted
Gorain B et al. A Randomized, Crossover Bioequivalence Study … Drug Res 2013; 63: 177–184
Original Article 179
from 1 h before dosing till 1 h after dosing and ad libitum thereaf-
ter. Panned meals of 2 400 Kcal were divided into lunch, snacks
and dinner and were provided after 4 h, 8 h and 13 h respectively
after drug ingestion. Venous blood samples were taken before and
at regular intervals after drug administration as described below.
Plasma concentrations of amlodipine, telmisartan and hydrochlo-
rothiazide were measured from each blood sample. Standard
pharmacokinetic parameters were calculated.
Blood sample collection
According to FDA and EMEA regulations, the sampling schedule
should be planned to provide a reliable estimate of the extent of
absorption. Usually the sampling time should extend to at least
3 terminal elimination half lives of the active ingredient. Time
periods between sampling should not exceed one terminal half
life [18]. A total of 19 blood samples (5 mL) were drawn one just
before the drug administration (pre-dose) and at 0.5, 1.0, 1.5,
2.0, 2.5, 3.0, 3.5, 4.0, 6.0, 6.5, 7.0, 7.5, 8.0, 12.0, 24.0, 48.0, 72.0, &
96.0 h post-dose in the vacutainer tubes containing EDTA. Col-
lected blood samples were centrifuged in cold, plasma was sepa-
Downloaded by: Chinese University of Hong Kong. Copyrighted material.
rated in ria vials and stored at deep-freezer ( − 20 °C) with
appropriate labeling.
Fig. 2 Study Flow chart.
180 Original Article
Analytical Procedure
▼ imum concentration (tmax), elimination rate constant (Kel) and
Chemicals and reagents
Working standards of amlodipine, telmisartan and hydrochloro-
thiazide were obtained from Akums Drugs and Pharmaceutical
Ltd., Delhi, India and metoprotol for use as internal standard was
obtained from Micro Labs, Tamilnadu, India. Ammonium for-
mate was purchased from S D Fine-Chem Limited (Mumbai,
India) and formic acid was purchased from Sisco Research Labo-
ratories Pvt. Ltd (Mumbai, India). Methanol (LC grade) was
obtained from Merck Private Limited (Mumbai, India). The water
used throughout the analysis was of HPLC grade, [resistivity of
18.2 MΩ cm that was generated by using a Milli-Q gradient sys-
tem of Millipore (Elix 3, Milli-Q A10 Academic)].
Procedure
A validated liquid chromatography/tandem mass spectrometry
(LC/MS/MS) method was used for the determination of
amlodipine, telmisartan and hydrochlorothiazide concentration
in human plasma. The liquid chromatographic separation was
performed using a Shimadzu scientific instruments (Shimadzu
Corporation, Kyoto, Japan) consisted of 2 LC-20AD delivery
pumps, an on-line DGU-20A3 prominence solvent degasser, and
column oven (CTO-10ASVP) along with auto-sampler (SIL-
20ACHT) and controller (CBM20A Lite) was used to inject 40 μL
aliquots of the processed samples on a Phenomenox Gemini C18
column, 50 mm × 4.6 mm, particle size 5 μm (Chromatopak,
India), which was maintained at room temperature. The
autosampler temperature was maintained at 10 ± 1 °C. An iso-
cratic mobile phase composition consisted of 10 mM ammo-
nium formate buffer (pH 7.5) and methanol (10:90, v/v),
delivered at a flow-rate of 0.5 mL/min was used for chromato-
graphic resolution of amlodipine, telmisartan, hydrochlorothi-
azide and metoprolol (IS). Quantitation of all the analytes and
the IS was achieved by MS-MS detection in positive (telmisartan,
amlodipine and the IS, metoprolol) and negative (hydrochloro-
thiazide) ion modes using a triple quadrupole mass spectrome-
ter (API 2000) made by AB Sciex Instruments (Toronto, Canada),
equipped with an electrospray ionization source operating in
positive ion mode and with a Turboionspray™ interface at
425 °C. Procedures of validation and acceptance criteria were
based on “FDA Bio-analytical Method validation guidelines”
[19]. 8 non-zero calibration standards with concentration rang-
ing from 1 to 50 ng/mL for amlodipine and 1 to 1 000 ng/mL for
telmisartan and hydrochlorothiazide were prepared by adding
100 μL of working solutions with 50 μL of IS solution (from
500 ng/mL) to 400 μL of drug free human plasma. The extraction
of the analytes and the IS were performed by adding upto 5.0 ml
of organic solvent of methyl tert-butyl ether and by hand mixing
for 10 min. The organic layer (4.0 mL) was separated after cen-
trifugation for 15 min at 5 000 rpm and it was evaporated to dry-
ness at 45 °C using a gentle stream of nitrogen. The residue was
reconstituted with 200 μL of the mobile phase and 40 μL were
injected onto LC-MS/MS system.
Pharmacokinetic and statistical analysis
After validation of the bio-analytical method, volunteer plasma
samples were processed and analyzed as described in the ana-
lytical procedure section and pharmacokinetics parameters like
area under the plasma-concentration-time curve from zero to
the last measurable plasma sample time and to infinity (AUC0-t
Gorain B et al. A Randomized, Crossover Bioequivalence Study … Drug Res 2013; 63: 177–184
and AUC0-∞), maximum concentration (Cmax), time to reach max-
elimination half-life (t1/2) for the period of 0.0–96.0 h by non
compartmental method were evaluated by using WinNonlinTM
Enterprise, Version: 5.3 software (Pharsight Corporation, Moun-
tain View, California). The test and the reference formulations
were considered to be bioequivalent if the calculated 90 % confi-
dence intervals (CI) for the log transformed ratios (test/reference)
of the Cmax, AUC0-t, and AUC0-∞ were within the bioequivalence
criteria range of 80.00–125.00 as established by the Central Drug
Standard Control Organization (CDSCO) [15], India; US Food and
Drug Administration (US FDA) [20] and European Medicines
Evaluation Agency (EMEA) [21].
Results
▼
No changes of the protocol were carried out after the start of the
study, and no major deviations from the protocol were observed.
The sensitivity and specificity of the assay were found to be suf-
Downloaded by: Chinese University of Hong Kong. Copyrighted material.
ficient for accurately characterizing the single dose bioequiva-
lence study of amlodipine 10 mg, telmisartan 80 mg and
hydrochlorothiazide 25 mg tablet was conducted in 24 adult
healthy, human, male volunteers in the fasting state. The 2 for-
mulations were well tolerated by the subjects participated in the
bioequivalence study. No adverse event was observed during
both the periods of the study in any of the subjects. Both clinical
and laboratory parameters of all subjects showed no clinically
significant changes. Product ion spectra and typical multiple
reaction monitoring chromatograms of the individual compo-
nents are shown in ● ▶ Fig. 3. ●
▶ Fig. 4–6 show that the plots of
mean plasma concentrations of test and reference formulations
of amlodipine, telmisartan and hydrochlorothiazide were
absorbed from the gastrointestinal tract when they were taken
under a fasting state. Mean pharmacokinetic parameters of
amlodipine, telmisartan and hydrochlorothiazide for the test
and the reference formulation, in 24 healthy Indian subjects are
presented in ● ▶ Table 1. The results of ANOVA revealed that none
of the basic pharmacokinetic parameters were influenced by
the FDC formulation for all the components analysed (● ▶ Table 1,
●
▶ Fig. 4–6).
The area under the plasma concentration time curve from time
zero to time t (AUC0–t) value for test and reference preparation of
amlodipine, telmisartan and hydrochlorothiazide were 161.484 ±
25.631 ng.h/mL and 162.108 ± 12.115 ng.h/mL, 1 917.644 ±
284.368 ng.h/mL and 2 014.764 ± 261.806 and 822.847 ±
54.291 ng.h/mL and 828 ± 46.747 ng.hr/mL, respectively. Maxi-
mum plasma concentration (Cmax) of test and reference formula-
tion ranged from 5.234 ± 0.914 ng/mL and 4.991 ± 0.563 ng/mL,
108.839 ± 13.601 ng/mL and 114.783 ± 12.315 ng/mL and 97.814 ±
10.779 ng/mL and 93.731 ± 10.018 ng/mL at the time 7.375 ±
0.557 h and 7.250 ± 0.511 h, 1.875 ± 0.516 h and 1.542 ± 0.464 h
and 2.369 ± 0.551 h and 1.938 ± 0.517 h for amlodipine, telmisar-
tan and hydrochlorothiazide respectively. Again, the values of
area under the plasma concentration–time curve from time zero
to infinity (AUC0–∞) were 219.747 ± 27.699 ng.h/mL and 230.567 ±
17.417 ng.h/mL, 2 824.618 ± 442.575 ng.h/mL and 2 984.991 ±
420.453 and 1 027.248 ± 59.004 ng.h/mL and 1 042.824 ±
60.460 ng.h/mL for the test and reference preparation of
amlodipine, telmisartan and hydrochlorothiazide.
 Original Article 181

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Fig. 3 Product ion spectra of a Amlodipine, b Telmisartan & c Hydrochlorothiazide and typical multiple reaction monitoring chromatograms of
a Amlodipine, b Telmisartan & c Hydrochlorothiazide.

Additionally the 90 % CI for the ratios of mean Cmax, AUC0-t, and
AUC0-∞ were within the range of 80.00–125.00 (using log trans-
formed data), meeting the regulatory criterion for bioequiva-
lence as mentioned above. ● ▶ Table 2 represents the ratio (test/
reference), 90 % CI and the intra-subject variations of the Cmax,
AUC0-t and AUC0-∞.
For overall extent of absorption, both the formulations were
equivalent, with test/reference formulation ratios of both AUC0-t
and AUC0-∞ very close to 100 %. Based on the plasma levels of the
24 completed subjects, the mean relative bioavailability of FDC
tablet containing amlodipine, telmisartan and hydrochloro-
thiazide were 99.62 %, 95.18 % and 99.22 % as compared with the
separate marketed reference products of those drugs.

Gorain B et al. A Randomized, Crossover Bioequivalence Study … Drug Res 2013; 63: 177–184
182 Original Article

Fig. 4 Mean plasma concentration-time profile

of amlodipine after single oral dose administration
for test and reference preparations in 24 healthy
human volunteers.

Downloaded by: Chinese University of Hong Kong. Copyrighted material.

Fig. 5 Mean plasma concentration-time profile
of telmisartan after single oral dose administration
for test and reference preparations in 24 healthy
human volunteers.

Fig. 6 Mean plasma concentration-time profile of

hydrochlorothiazide after single oral dose admin-
istration for test and reference preparations in 24
healthy human volunteers.

Discussion the bioequivalence of a FDC tablet formulation (batch number

▼ PPT – 662A; manufacturing by Akums Drugs & Pharmaceuticals
This is the first bioequivalence study to establish the effect of the Ltd., Delhi, India) with the tablet Amlogard-10 (containing
FDC combination of amlodipine, telmisartan and hydrochloro- amlodipine 10 mg) manufactured by Pfizer Pharmaceutical India
thiazide conducted on Indian population. This study assessed Pvt. Ltd., India, tablet Telday (containing telmisartan 80 mg)

Gorain B et al. A Randomized, Crossover Bioequivalence Study … Drug Res 2013; 63: 177–184
 Original Article 183

Table 1 Pharmacokinetic parameters of amlodipine, telmisartan and hydrochlorothiazide in healthy human volunteer following oral dosing of F.D.C. tablet
of amlodipine 10 mg, telmisartan 80 mg and hydrochlorothiazide 25 mg (Test) and Reference preparations, individual tablets of Amlogard-10 (containing am-
lodipine 10 mg), Telday (containing telmisartan 80 mg and tablet Aquazide (containing hydrochlorothiazide 25 mg).

Pharmacokinetic parameters Amlodipine Telmisartan Hydrochlorothiazide

Test Reference Test Reference Test Reference
AUC0-t (ng.h/mL) Mean 161.484 162.108 1 917.644 2 014.764 822.847 829.323
± SD 25.631 12.115 284.368 261.806 54.291 46.747
AUC 0-∞ (ng.h/mL) Mean 219.747 230.567 2 824.618 2 984.991 1 027.248 1 042.824
± SD 27.699 17.417 442.575 420.453 59.004 60.460
Cmax (ng/mL) Mean 5.234 4.991 108.839 114.783 97.814 93.731
± SD 0.914 0.563 13.601 12.315 10.779 10.018
Tmax (h) Mean 7.375 7.250 1.875 1.542 2.396 1.938
± SD 0.557 0.511 0.516 0.464 0.551 0.517
Kel Mean 0.020 0.019 0.029 0.029 0.082 0.080
± SD 0.002 0.002 0.003 0.003 0.005 0.006
t1/2 (h) Mean 34.201 37.337 24.008 23.877 8.512 8.695
± SD 3.171 3.197 2.340 2.340 0.489 0.631
Relative bioavailability ( %) 99.62 100.00 95.18 100.00 99.22 100
Cmax, maximum plasma concentration; tmax, time require to achieve maximum concentration; AUC0–t, area under the plasma concentration time curve from time zero to t h;
AUC0–∞, plasma concentration–time curve from time zero to infinity; t1/2 (h), elimination half life; Kel, elimination rate constant

Downloaded by: Chinese University of Hong Kong. Copyrighted material.

Table 2 90 % confidence interval with the Test preparation of F.D.C. tablet containing amlodipine 10 mg, telmisartan 80 mg and hydrochlorothiazide 25 mg
(Test) and Reference preparations, individual tablets of Amlogard-10 (containing amlodipine 10 mg), Telday (containing telmisartan 80 mg and tablet Aquazide
(containing hydrochlorothiazide 25 mg).

Confidence Interval Amlodipine Telmisartan Hydrochlorothiazide

Cmax Untransformed data 91.22–119.25 85.35–102.56 96.77–110.85
Ln transformed data 94.38–110.69 97.17–100.44 99.26–102.56
AUC0-t Untransformed data 89.12–110.03 82.49–105.81 95.48–103.02
Ln transformed data 97.90–101.59 98.01–100.60 99.30–100.45
AUC0-∞ Untransformed data 86.37–103.45 81.38–106.16 95.15–102.01
Ln transformed data 97.56–100.48 97.90–100.64 99.27–100.30

manufactured by Torrent Pharmaceutical Ltd, India and Tablet Acknowledgement

Aquazide (containing hydrochlorothiazide 25 mg) manufac-
tured by Sun Pharmaceuticals Industries Ltd., India, establishing
that the FDC combination can be effectively prescribed to the
patients with essential hypertension.
Triple drug combination of amlodipine, telmisartan and hydro-
chlorothiazide may serve a potential role in achieving desired BP
goals, in patients with essential hypertension, which are other-
wise poorly managed by either monotherapy or dual drug ther-
apy [4, 8, 9].
The combination of all the 3 drugs was found to be well tolerated
in the present study. No adverse effects were reported or
observed in any of the subjects. This finding is consistent with
previously published clinical study by Maladkar et al. where it is
shown that the combination is well tolerated in the treatment of
essential hypertension [4].
In summary this study has demonstrated the bioequivalence of
the fixed dose combination (FDC) product of amlodipine 10 mg,
telmisartan 80 mg and hydrochlorothiazide 25 mg tablet and
the reference products of tablet Amlogard-10 (containing
amlodipine 10 mg) manufactured by Pfizer Pharmaceutical India
Pvt. Ltd., India, tablet Telday (containing telmisartan 80 mg)
manufactured by Torrent Pharmaceutical Ltd, India and Tablet
Aquazide (containing hydrochlorothiazide 25 mg) manufactured
by Sun Pharmaceuticals Industries Ltd. Hence it can be con-
cluded that the fixed dose formulations can be used interchange-
ably in essential hypertension instead of individual products to
serve the same purpose with better convenience and compli-
ance to the patients with essential hypertension.
▼
The authors are thankful to Department of Science and Technol-
ogy (DST) under DPRP, New Delhi, Govt. of India, for providing
the financial assistance through there project No. VI-D&P/
312/09-10-TDT. We are grateful to Akums Drugs and Pharma-
ceutical Ltd., Delhi, India for supplying drug as a gift sample. We
are very much thankful to Bioequivalence Study Center, Jadavpur
University for providing the necessary facilities.
Conflict of Interest
▼
The authors confirm that this article content has no conflicts of
interest.
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