JAC Advance Access published online on September 20, 2002
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkf172
© 2002 by The British Society for Antimicrobial Chemotherapy
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Original Paper
1 Department of Chest and
Infectious Diseases, Hospital Heckeshorn-Zehlendorf, Berlin
* Corresponding author. E-mail: haloheck{at}zedat.fu-berlin.de.
Received 22 March 2002
; revised 14 May 2002
; accepted 9 July 2002
In a randomized, double-blind, placebo-controlled,
four-way crossover study, possible influences of the triple therapy
with amoxicillin, clarithromycin and the proton pump inhibitor lansoprazole on
the pharmacokinetics of each of the drugs and the active 14-OH-clarithromycin
metabolite were assessed. Twelve Helicobacter pylori-negative
healthy male volunteers (age 27 ± 4.3
years; creatinine clearance 7.0 ± 2.0
L/h) were given lansoprazole 30 mg, amoxicillin 1 g and clarithromycin
500 mg, alone and in triple combination. Drug elimination intervals
were at least 9 days between the dosing periods. The study medication
was administered twice daily for 4 days. On the fifth day of each
period, drugs were only given once in the morning, and blood and
urine samples were collected for 12 h. The concentrations of the
three substances administered, and 14-OH-clarithromycin, were determined
by validated HPLC methods. Alterations in the serum kinetics were
found for lansoprazole and the active 14-OH-clarithromycin metabolite
(all data expressed as mean ± ).
For lansoprazole, the elimination half-life (t1/2)
was significantly prolonged (1.46 versus 1.7 h, P < 0.05)
and the area under the concentration-time curve from 0
to 8 h (AUC0-8) was significantly increased
(3.65 versus 4.59 mg·h/L, P < 0.05)
by combination of the drugs. For 14-OH-clarithromycin, the peak
concentration (Cmax) was 0.95 versus
1.18 mg/L and the AUC from 0 to 12 h (AUC0-12)
was 8.3 versus 10.5 mg·h/L (augmented significantly, P < 0.05). The amoxicillin concentrations
were slightly elevated by concomitant administration of lansoprazole
and clarithromycin but without statistical significance (11.1 versus
12.6 mg/L). For clarithromycin, the time to maximum concentration
of drug in serum (Tmax) was increased
(2.73 versus 3.31 h, P < 0.05),
whereas AUC and Cmax remained unchanged.
Simultaneous administration of lansoprazole, amoxicillin and clarithromycin
increases the serum concentrations of lansoprazole and the active
14-OH-clarithromycin metabolite significantly. These effects were
not so pronounced as to have any therapeutic influence, making dosage
adjustment unnecessary.
Pharmacokinetics of lansoprazole, amoxicillin and
clarithromycin after simultaneous and single administration
2 Klinikum Benjamin Franklin, Freie
Universität Berlin, Berlin, Germany
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