JAC Advance Access originally published online on September 20, 2002
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Journal of Antimicrobial Chemotherapy (2002) 50, 699-706
© 2002 The British Society for Antimicrobial Chemotherapy
Pharmacokinetics of lansoprazole, amoxicillin and clarithromycin after simultaneous and single administration
1 Department of Chest and Infectious Diseases, Hospital Heckeshorn-Zehlendorf, Berlin; 2 Klinikum Benjamin Franklin, Freie Universität Berlin, Berlin, Germany
Received 22 March 2002; returned 14 May 2002; revised 27 June 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 ± S.D.). 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.
* Correspondence address. Department of Pulmonary and Infectious Diseases, City Hospital Berlin-Heckeshorn, affil. Freie Universität Berlin, Zum Heckeshorn 33, 14109 Berlin, Germany. Tel: +49-30-8002-2222; Fax: +49-30-8002-2623; E-mail: haloheck{at}zedat.fu-berlin.de