PMID- 7712674
OWN - NLM
STAT- MEDLINE
DCOM- 19950516
LR  - 20131121
IS  - 0009-9236 (Print)
IS  - 0009-9236 (Linking)
VI  - 57
IP  - 4
DP  - 1995 Apr
TI  - Pharmacokinetics and pharmacodynamics of neutrophil-associated ciprofloxacin in 
      humans.
PG  - 446-54
AB  - OBJECTIVE: To study the possibility that the penetration of the antibiotic 
      ciprofloxacin into polymorphonuclear leukocytes (PMN) may be associated with some 
      changes in cell reactivity. DESIGN: Superoxide anion and chemiluminescence 
      generation induced by formyl-methionyl-leucyl-phenylalanine (fMLP) and 
      platelet-activating factor (PAF) were studied ex vivo in 12 healthy volunteers 
      (mean age, 53.15 +/- 16.3 years; mean body weight, 71.23 +/- 6.9 kg) at fixed 
      intervals up to 72 hours from the administration of a single oral dose of 250 mg 
      ciprofloxacin. Cytosolic free calcium levels ([Ca2+]i) in resting and stimulated 
      cells were also evaluated. The dynamic parameters of the effects on PMNs were 
      compared with the kinetic profile of the drug in plasma and in PMNs. RESULTS: 
      Superoxide generation induced by the stimulating agents increased significantly, 
      reaching a peak after 12 hours (+116% [p < 0.001] for fMLP and +66% [p < 0.05] 
      for PAF). Similarly, chemiluminescence production showed a threefold increase in 
      the response to the stimulating agents 12 hours after drug administration (p < 
      0.001). The increase in [Ca2+]i in stimulated PMNs was significantly potentiated 
      (p < 0.001). The mathematic analysis of the effects of ciprofloxacin showed that 
      time to maximal activity was between 10.4 hours (PAF-dependent [Ca2+]i increase), 
      and 15 hours (fMLP-induced superoxide anion and chemiluminescence production). 
      The ratio of PMNs to plasma ciprofloxacin concentration increased progressively, 
      from 0.5 at 30 minutes to 10.4 after 24 hours. In addition, time to maximal 
      activity and half-life differed in PMNs and in plasma (4.66 versus 1.90 hours and 
      13.03 versus 7.28 hours, respectively). CONCLUSIONS: Ciprofloxacin administration 
      induced a long-lasting enhancement of PMN reactivity to fMLP and PAF. The levels 
      of the drug in the cells were greater and more sustained in the time than those 
      in plasma.
FAU - Capecchi, P L
AU  - Capecchi PL
AD  - Institute of Clinical Medicine, University of Siena, School of Medicine, Italy.
FAU - Blardi, P
AU  - Blardi P
FAU - De Lalla, A
AU  - De Lalla A
FAU - Ceccatelli, L
AU  - Ceccatelli L
FAU - Volpi, L
AU  - Volpi L
FAU - Pasini, L
AU  - Pasini L
FAU - Di Perri, T
AU  - Di Perri T
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PL  - United States
TA  - Clin Pharmacol Ther
JT  - Clinical pharmacology and therapeutics
JID - 0372741
RN  - 0 (Platelet Activating Factor)
RN  - 59880-97-6 (N-Formylmethionine Leucyl-Phenylalanine)
RN  - 5E8K9I0O4U (Ciprofloxacin)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Analysis of Variance
MH  - Ciprofloxacin/blood/pharmacokinetics/*pharmacology
MH  - Female
MH  - Half-Life
MH  - Humans
MH  - Luminescent Measurements
MH  - Male
MH  - Middle Aged
MH  - N-Formylmethionine Leucyl-Phenylalanine/pharmacology
MH  - Neutrophils/drug effects/*metabolism
MH  - Platelet Activating Factor/pharmacology
MH  - Time Factors
EDAT- 1995/04/01 00:00
MHDA- 1995/04/01 00:01
CRDT- 1995/04/01 00:00
PHST- 1995/04/01 00:00 [pubmed]
PHST- 1995/04/01 00:01 [medline]
PHST- 1995/04/01 00:00 [entrez]
AID - 10.1016/0009-9236(95)90215-5 [doi]
PST - ppublish
SO  - Clin Pharmacol Ther. 1995 Apr;57(4):446-54. doi: 10.1016/0009-9236(95)90215-5.