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ISSN 0303 - 7932

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FOLIA MEDICA
IN DON ESIAN A
Vol. 44 No. 4 October

- December 2008

GENETIC VARIATION OF G6PD AND ADAPTIVE PHENOMENA IN MALARIAL INFECTION
(Indah S Tantular)
MOLECULAR ANALYSIS OF THE CODING SEQUENCE OF MAGE-1 GENE FROM HEPATOCELULA
CARCINOMA PATIENT AND TESTIS
(Gondo Mastutik et al)

POTENTIAL VALUE OF C-REACTIVE PROTEIN AS INFLAMMATION MARKER AND IL-lfr TNF-a
AS PRO INFLAMMATORY CYTOKINE ON DISEASE ACTIVITY OF RHEUMATOID ARTHRITIS
(FM Judajana)
HER2-NEU SURFACE CELL ONCOPROTEIN EXPRESSION IN BREAST DUCTAL CARCINOMA

(Imam Susilo)
DIFFERENCE IN THE PRODUCTIVITY OF B-LYMPHOCYTE ISOLATED FROM LYMPH NODES
AND THAT ISOLATED FROM MICE SPLEEN IN THE PRODUCTION OF TOXOCARA CATI MONOCLONAL
ANTIBODY USING HYBRIDOMA TECHNOLOGY
(I Ketut Sudiana)
EXPLORATION IN THE USE OF MEDICINAL PLANT ACANTUS ILICIFOUUS L IN THE TREATMENT
OF ENDOTHELIAL DYSFUNCTION
(I Ketut Sudiana, Elyana Asnar, Sunarko Setyawan, Heru Kusbianto)

DETECTION OF M. TUBERCULOSIS AND DRUG SENSITIVITY TEST FROM SPUTUM CULTURE OF
PULMONARY TUBERCULOSIS PATIENTS IN DR SOETOMO GENERAL HOSPITAL BETWEEN 2003-2004
(Justinus Frans Palilingan)

THE PHARMACOKENETICS OF LEVOFLOXACIN IN HEALTHY RABBIT TREATED WITH ANTACID
(Aniek Sedya Budiatin, Weni Kristanti, Suharjono)
POTENCY OF LACTOBACILLUS REUTERI ON REDUCED INFLAMMATION IN SEPTIC ENCEPHALOPATHY
(OS Hartanto, Diding HP)

•K.

PHARMACOKINETIC PARAMETERS DETERMINATION OF A SINGLE 500-MG ORAL DOSE
OF LEVOFLOXACIN IN HEALTHY SUBJECTS BY USING BLOOD DATA
(Toetik Aryani, Suharjono, Febri Hari Murti)
ENCEPHALOPATHY AND NEUROENDOCRINE DISORDER IN SEPTIC SHOCK
(OS Hartanto)
OSTEOARTH RITIC PAIN TREATMENT WITH ELECTROACUPUNCTURE
(Zainai Arifin A)

Review Artide and Clinical Experience:
ASTAXANTHIN - OXIDATIVE STRESS - DIABETES MELLTTUS
From Basics to Clinics and from General to Spetific
(Askandar Tjokroprawiro)

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Surabaya
Oct- Dec 2008

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FOLIA MEDICA INDONESIANA
ISSN 0303 - 7932

Vol. 44 No. 4 October - December 2008

CONTENTS
GENETIC VARIATION OF G6PD AND ADAPTIVE PHENOMENA IN MALARIAL INFECTION
(Indah S Tantular)

MOLECULAR ANALYSIS OF THE CODING SEQUENCE OF MAGE-1 GENE FROM HEPATOCELULAR

CARCINOMA PATIENT AND TESTIS

(Gondo Mastutik et al)

216-223

224 - 232

POTENTIAL VALUE OF C-REACTIVE PROTEIN AS INFLAMMATION MARKER AND IL-ip, TNF~a
AS PRO INFLAMMATORY CYTOKINE ON DISEASE ACTIVITY OF RHEUMATOID ARTHRITIS
(FM Judajana)

233 - 241

HER2-NEU SURFACE CELL ONCOPROTEIN EXPRESSION IN BREAST DUCTAL CARCINOMA
(Imam Susilo)

242 - 250

DIFFERENCE IN THE PRODUCTIVITY OF B-LYMPHOCYTE ISOLATED FROM LYMPH NODES

AND THAT ISOLATED FROM MICE SPLEEN IN THE PRODUCTION OF TOXOCARA CATI MONOCLONAL
ANTIBODY USING HYBRIDOMA TECHNOLOGY
(I Ketut Sudiana)

251 - 254

EXPLORATION IN THE USE OF MEDICINAL PLANT ACANTUS ILICIFOLIUS L IN THE TREATMENT
OF ENDOTHELIAL DYSFUNCTION
(I Ketut Sudiana, Elyana Asnar, Sunarko Setyawan, Heru Kusbianto)

255 - 258

DETECTION OF M. TUBERCULOSIS AND DRUG SENSITIVITY TEST FROM SPUTUM CULTURE OF
PULMONARY TUBERCULOSIS PATIENTS IN DR SOETOMO GENERAL HOSPITAL BETWEEN 2003-2004
(Justinus Frans Palilingan)

259 - 263

THE PHARMACOKENETICS OF LEVOFLOXACIN IN HEALTHY RABBIT TREATED WITH ANTACID
(Aniek Setiya Budiatin, Weni Kristanti, Suharjono)

264 - 268

POTENCY OF LACTOBACILLUS REUTERI ON REDUCED INFLAMMATION IN SEPTIC ENCEPHALOPATHY
(OS Hartanto, Diding HP)

269 - 273

PHARMACOKINETIC PARAMETERS DETERMINATION OF A SINGLE 500-MG ORAL DOSE
OF LEVOFLOXACIN IN HEALTHY SUBJECTS BY USING BLOOD DATA
(Toetik Aryani, Suharjono, Febri Hari Murti)

274 - 280

ENCEPHALOPATHY AND NEUROENDOCRINE DISORDER IN SEPTIC SHOCK
(OS Hartanto)

281 - 284

OSTEOARTHRITIC PAIN TREATMENT WITH ELECTROACUPUNCTURE
(Zainal Arifin A)

285 - 292

Review Article and Clinical Experience:
ASTAXANTHIN - OXIDATIVE STRESS - DIABETES MELLITUS
From Basics to Clinics and from General to Specific
(Askandar Tjokroprawiro)

293 - 299

The Pharmacokenetics of Levofloxacin in Healthy Rabbit Treated with Antacid (Aniek Setiya Budialin, Weni Kristanti, Suhaijo

THE PHARMACOKENETICS OF LEVOFLOXACIN IN HEALTHY RABBIT
TREATED WITH ANTACID
Aniek Setiya Budiatin, Weni Kristanti, Suharjono
Departement of Clinical Pharmacy.
Airlangga University School of Pharmacy.
Surabaya.

ABSTRACT

The effect of antacid (Antasida DOEN) 14 ml/ kgBW which containing polyvalent cation Mg (OH)2 and Al(OH) 3 on
absorption of levofloxacin were examined in healthy rabbit. Twelve subjects were administered 23 mg/ml kg B
levofloxacin alone. On day 8 the six subjects were administered antacid and levofloxacin concomitant and the oth
were administered antacid two hours after levofloxacin. There were statistically significant different in pharmacokine
parameter produced by administration with antacid concomitant but the other one were not significant different. Th
were CmttX and AUC decrease (p0.05) for administrati
concomitant and but the other one were C
AUC and tnmx smaller than control but not significant different (p>0.0
The different had apparent effect on the plasma concentrations of levofloxacin and was determined w
spectrofiuorometric.Antacid may reduce the absorption of levofloxacin, the extent of this interaction appears
increase as time between administration of two drugs decreases.
Keyword: levofloxacin, Mg (OH)2 and Al(OH) 3 antacid, spetrofluorometric

Correspondence: Aniek Setiya Budiatin, Departement of Clinical Pharmacy, Airlangga University
School of Pharmacy, J1 Dharmawangsa Dalam, Surabaya, phone. 62-31-5033710

INTRODUCTION

Levofloxacin (fig. 1) is fluoroquinolone antibiotic and is
the 1 ofloxacin isomer, more active 8-128 times
against positive and negative microorganism than dofloxacin, and twice more potent than rasemat form
(Fish and Chow, 1997). Levofloxacin were used for
treatment disease : GIT, respiratory tract up and down;
urinary tract, skin infection, which inhibit DNA
synthesis as a potential antibacterial. Plasma
concentrations in healthy volunteers reach a mean peak
drug plasma concentrations (Cmax) of approximately 2.8
and 5.2 mg/L within 1 to 2 hours after oral
administration of levofloxacin 250 and 500 mg tablets,
respectively. The oral absorption is very rapid and
complete, the bioavailability of oral levofloxacin
approaches 100% and it little affected by administration
with food (Fish and Chow, 1997).

HN
N

KJ

,N

CH3

.N.

F

COOH
O

Figure 2. Ciprofloxacin

In separate study, the effect of antacid, sucralfat; foo
H2 receptor antagonist on fluoroquinolon interacti
was examined (Radanst et al. 1992). The interactio
with aluminum and magnesium containing antacid w

fluoroquinolones (siprofloxacin, Figure 2), resulting
significantly decrease absorption when administer
concurrently (Fish and Chow 1997). A measure such
ttna* does not adequately describe situations in whi
double peaking may occur or which prolong
absorption is observed. Antacid (Mg (OH)2 and Al(O
3) is widely used for a variety of indications (duoden
ulcer disease, dyspepsia, saur stomach) (McEvoy 200
The probably that levofloxacin will be given to patie
receiving long term therapy with antacid/H2 blocker
high. Since antacid affect oral absorption of variety

O

C02H

F.

Y

CH3

Figurel. Levofloxacin

264

Folia Medica Indonesiana Vol. 44 No. 4 October - December 2008 : 264-268

agents, the effect of administration of antacid on the
absorption of ciprofloxacin was studied (Radanst et al,
1992), Therefore studies were perform to determined
the effect of antacid administration on the oral
absorption of levofloxacin in healthy rabbits.

One milliliter of the ammonium molybdenum solution
(7.5 |ig /ml) was added and pH was adjusted to 3.5
using 1 ml of Teorell and Stenhagen buffer solution.
The volume was completed with methanol. The relative
fluorescence intensity of resulting solutions was
measured against reagent blanks treated similarly at the
excitation and emission maxima specified for
levofloxacin. (El-Kommos et al. 2003)

MATERIAL AND METHODS
Levofloxacin was a kind gift of PT Kimia Farma.
Methanol (HPLC gradient) was purchased from JT
Baker, Antacida DOEN was a kind gift of First
Medipharma, Dipotassium hydrogenphosphate and
Phosphoric acid 85% were purchased from Merck
(Darmstadt, Germany), Double distilled Water was
obtained from PT. Ikapharmindo Putramas (Indonesia).
Heparin 500 unit/ml, Ammonium molybdat were
purchased from Fluka AG, Citric acid was purchased
from Riedel-de Haen. Xylol was obtained from Brataco
Chemika, Acetonitril was purchased from Riedel-de
Haen, Hitachi F-4000 Spectrofluorometer (Japan) was

Five milliliter of plasma were deproteinized by the
addition of 10 ml acetonitrile, centrifuged at 4000 rpm
for 5 minutes. One milliliter of clear supernatant was
spiked with 1 ml of drug stock solution. The mixture
was then extracted with 2 portions; each of 5 ml
chloroform. The chloroformic extract was collected,
evaporated on a boiling water bath, then appropriate
dilutions were made to obtain drug solutions containing
100, 300 and 500 ng/ ml, then general procedure was
followed. The twelve rabbits were the same treatment as
levofloxacin alone, and the day 8, six rabbits were
administered antacid and levofloxacin concomitant and
the other one were administered antacid 2 hours after
levofloxacin (El-Kommos et. al., 2003).

used for fluorometric measurements, Direct Reading
Micro Balance LM -20 Libror, Ultrasonic Cleaner
Sakura US-10E, Centrifuge Hettich, Protofix 32,
Thermolyne Bamstead type 37600, glassware and
injection syringe.

The pharmacokinetic analysis of plasma concentration
of
using
levofloxacin
determined
were
spectrofluorometric method. The assay had a dynamic
range of 10 to 60 ng/ml (El-Kommos et al. 2003). . The
maximum plasma concentration of levofloxacin (C,nax)
and earliest time at which Cmax occurred (tlnax) were
estimated directly from the experimental data. The
intensity under the plasma concentration-time curve
from time zero to the last time (t) plasma levofloxacin
was measurable (AUC 0.300) was estimated by the linier
trapezoidal approximation (Shargel 2005). Student’s t
tests with 95% confidence limits were used to examine
pair-wise differences between the groups. Value of
p0.05). It’s
suggested that levofloxacin dose are separated from
antacid dose by more than 2 hours.

on the absorption of ciprofloxacin’, Clin Pharmacol
Ther, no. 46, pp. 700-705.
Paget, GE. and Barnes, JE 1964, ‘ Toxicity test’, in DR
Laurence, AL Bacharach, Evaluation of Drugs
Activities: Pharmacometrics, vol. I, Academic Press,
London, pp. 161.
Radanst, JM, Marchbanks CR, Dudley, MN, 1992,
interaction of fluoroquinolones with other drugs:
mechanism, variability, clinical significance and
management’, Clinical Infectious Disease, vol. 14, no.
13, pp. 272-282.
Santosa, PB and Ashari, 2005, Analisis Statistik dengan
Microsoft Excel dan SPSS, 1st edn, Andi Offset,
Yogyakarta, pp. 60-62.
Shargel, L, Wu Pong, Susana, Yu, ABC 2005, Applied
Biopharmaceutics and Pharmacokinetics, 5th edn, The
McGraw-Hill Companies, Inc., Boston, pp. 453-477,
488.

REFERENCES

Brighty, Katherine, E. Gootz, Thomas D, 2000,
‘ Chemistry and mechanism of action of the quinolone
antibacterials’, in VT Andriole (ed), The Quinolones,
Academic Press, London, pp. 43-44.
El-Kommos, ME, Saleh, GA, El-Gizawi, SM, AbouElwafa, MA 2003, ‘ Spectrofluorometric determination
of certain quinolone antibacterials using metal
chelation', Talanta, vol. 60. pp. 1033-1050
Evans, G 2004, A Handbook of Bioanalysis and Drug
Metabolism, USA: CRC Press, pp 26

268