Influence of age on the steady state disposition of drugs commonly used for the eradication of Helicobacter pylori.
BACKGROUND
The success of eradication therapy for Helicobacter pylori might be affected by the age of patients.


OBJECTIVE
To investigate whether disposition of drugs commonly used for H. pylori eradication is age-dependent.


METHODS
Trough steady state serum levels of lansoprazole or ranitidine, amoxycillin, clarithromycin and metronidazole were monitored in 232 patients during the last dosing interval of a 5-day quadruple H. pylori eradication regimen. Detailed pharmacokinetic analysis was performed in 28 patients.


RESULTS
Linear correlations between age and trough serum levels were observed with lansoprazole (r=0.25; P=0.002), ranitidine (r=0. 38; P=0.001) and clarithromycin (r=0.36; P < 0.0001). These associations were also inversely dependent of creatinine clearance for ranitidine (r=0.36; P=0.001) and clarithromycin (r=0.30; P < 0. 0001). Multiple linear regression revealed age as an important factor influencing trough serum levels of lansoprazole, clarithromycin and ranitidine. There were significant inverse relationships between creatinine clearance and area under curve of ranitidine (r=0.88; P < 0.0001) and amoxycillin (r=0.56; P=0.002). Multiple linear regression revealed serum creatinine as the most important factor influencing the area under curve of ranitidine, clarithromycin and amoxycillin.


CONCLUSIONS
Age per se has little influence on pharmacokinetics of amoxycillin and ranitidine, which depend more on age-dependent decline in renal function. The influence of age, but not renal function was established for lansoprazole. Age and renal function have independent impacts on clarithromycin disposition.
Ammon
S
S
Dr Margarete Fischer-Bosch Institute of Clinical Pharmacology and Robert Bosch Hospital, Stuttgart, Germany. susanne.ammon@ikp-stuttgart.de
Treiber
G
G
Kees
F
F
Klotz
U
U
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000367:Age Factors; D000368:Aged; D000658:Amoxicillin / Q000493:pharmacokinetics; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics*; D017291:Clarithromycin / Q000493:pharmacokinetics; D003404:Creatinine / Q000378:metabolism; D005260:Female; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000378:metabolism; D016480:Helicobacter pylori / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000502:physiology; D064747:Lansoprazole; D008297:Male; D008795:Metronidazole / Q000493:pharmacokinetics*; D008875:Middle Aged; D009853:Omeprazole / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D010406:Penicillins / Q000493:pharmacokinetics; D011899:Ranitidine / Q000493:pharmacokinetics
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000900:Anti-Bacterial Agents; D000897:Anti-Ulcer Agents; D010406:Penicillins; D064747:Lansoprazole; D008795:Metronidazole; D000658:Amoxicillin; D011899:Ranitidine; D003404:Creatinine; D017291:Clarithromycin; D009853:Omeprazole