[Influence of ion pump-inhibiting drugs on the accumulation of ofloxacin and grepafloxacin in human polymorphonuclear leukocytes].
In this study we tested the influence of three ion pump-inhibiting drugs (digoxin, omeprazole and verapamil) on the accumulation of ofloxacin and grepafloxacin in human polymorphonuclear leukocytes. Two assay conditions were established: cell preincubation with the drug for 30 or 60 minutes before addition of quinolone, or addition of both drugs simultaneously. The maximum I/E for ofloxacin is different depending on the assay conditions: 7.69+/-0.88; 5.64+/-1.91 and 3.56+/-1.04 for the assay without preincubation and with preincubation for 30 or 60 minutes at 37 masculine C, respectively. Similarly, grepafloxacin reached the following maximums: 61.27+/-3.04; 32.18+/-3.25 and 22.52+/-3.86. Digoxin did not significantly modify the accumulation of the quinolones, but it increased the I/E compared with the control. In general, omeprazole reduced the accumulation of both quinolones. When omeprazole and ofloxacin were added together, ofloxacin's I/E was significantly lower; however, for grepafloxacin, 60 minutes of preincubation were necessary. Verapamil induced a significant increase in the I/E for both quinolones when the cells were preincubated at 10 times the plasma concentration.
Orero
A
A
Servicio de Microbiología, Unidad de Bacteriología Experimental, Centro de Investigación, Hospital Universitario La Fe, Avda. Campanar 21, 46009 Valencia, Spain.
Cantón
E
E
Pemán
J
J
Velert
M M
MM
Bermejo
M V
MV
D000890:Anti-Infective Agents / Q000493:pharmacokinetics*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004077:Digoxin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D024841:Fluoroquinolones; D006801:Humans; D016623:Ion Pumps / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000378:metabolism*; D015242:Ofloxacin / Q000493:pharmacokinetics*; D009853:Omeprazole / Q000494:pharmacology; D010879:Piperazines / Q000493:pharmacokinetics*; D014700:Verapamil / Q000494:pharmacology
D000890:Anti-Infective Agents; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D024841:Fluoroquinolones; D016623:Ion Pumps; D010879:Piperazines; D004077:Digoxin; D015242:Ofloxacin; D014700:Verapamil; D009853:Omeprazole; C075375:grepafloxacin