Ciprofloxacin pharmacokinetics

Nouaille-Degorce B, Veau C, Dautrey S,Tod M, Laouari D, Carbon C, et al. Influence of renal failure on ciprofloxacin pharmacokinetics in rats. Antimicrobial agents and chemotherapy. 1998 Feb 42(2) 289-92. 

Noer BL, Angaran DM. The effect of enteral feedings on ciprofloxacin pharmacokinetics. Pharmacotherapy ( 990) 10, 254. 

Frost RW, Carlson JD, Dietz AJ, Heyd A, Lettieri JT. Ciprofloxacin pharmacokinetics after a standard or high-fat/high-calcium breakfast. J Clin Pharmacol (1989) 29,953-5. 

Prince RA, Liou W-S, Kasik JE. Effect of cimetidine on ciprofloxacin pharmacokinetics-... 

Further development in the chemistry of oxazolidinone antibacterials was based mainly on the assumption that the 4-pyridyl moiety of one of Dupont s lead compounds, E-3709, might be amenable to replacement by suitably saturated heterocyclic bioisosteres [48]. This assumption was based on an example in which successful replacement of the piperazine ring system in the quinolone antibacterials, such as ciprofloxacin, with a pyridine fragment, such as seen in Win-57273, results in improvement of both the antibacterial and the pharmacokinetic profiles of the compounds. Similarly, as in the case of ciprofloxacin and Win-57273, it was predicted that the presence of a small but highly electron-withdrawing fluorine atom would be tolerated at the meta position(s) of the central phenyl ring, and would confer enhanced antibacterial activity and/or other desirable properties to the targeted oxazolidinones, as shown in Fig. 3. 

Webb MS, Boman NL, Wiseman DJ, et al. Antibacterial efficacy against an in vivo Salmonella typhimurium infection model and pharmacokinetics of a liposomal ciprofloxacin formulation. Antimicrob Agents Chemother 1998 42 45. 

The quinoline antibiotics are relatively late arrivals on the antibiotic scene. The parent compound of this class of drugs is nalidixic acid. The downside of this molecule is the rapid development of resistance by pathogenic bacteria. A major step forward was the introduction of a single fluorine atom at a key position, to yield new molecules such as ciprofloxacin, ofloxacin, levofloxacin, andmoxifloxacin. Of these, levofloxacin and moxifloxacin have the best combinations of spectrum of action, potency, and pharmacokinetic properties. In time, they are likely to largely replace the current quinoline antibiotic of choice, ciprofloxacin. Since these molecules work by a different mechanism than do the p-lactams, organisms that become resistant to the latter are generally susceptible to the former. 

Campoli-Richards D.M., J.P. Monk, and A. Price (1988). Ciprofloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 35 373 147. 

In terms of pharmacokinetics, 70-80% of orally administered ciprofloxacin (1) is absorbed by the Gl tract. It takes 0.5-1.0 h to reach a peak concentration, with a terminal half-hfe of 3.0-4.0 h. After oral administration, absorption was sufficient, and the absolute bioavailability varied between 63% to 77%. 

The pharmacokinetics of enrofloxacin and its active metabolite, ciprofloxacin, have been further extensively studied in sea bass after treatment by oral gavage or water, at a temperature of 15 C (157). Enrofloxacin was absorbed and eliminated slowly after oral administration to the sea bass. Following bath treatment, enrofloxacin efficiently penetrated fish tissues but it was poorly metabolized compared with mammals. On the other hand, ciprofloxacin was generally detected in very low concentrations (less than 0.02 ppm) in plasma samples after both oral and bath treatment. Liver levels of ciprofloxacin were found to be 0.12 ppm after a 5 ppm bathing for 24 h, 0.06 ppm after a 10 ppm bathing for 8 h, and 0.33 ppm after a 50 ppm bathing for 4 h, suggestive of hepatic metabolism of enrofloxacin. 

Dilger, C. Pharmacokinetics of ciprofloxacin gastric retentive tablets in healthy volunteers. CRS 28th Annual Meetings, San Diego, CA, 2001. 

Introduction of the first fluorinated quinolone, norfloxacin [nor FLOX a sin], has been rapidly followed by new members of this class. These agents are totally synthetic and are closely related structurally to an earlier quinolone, nalidixic acid [nal i DIX ik]. The principal member of this group is ciprofloxacin [sip ro FLOX a sin], which has the widest clinical application. Other antibiotics in this group available in the United States are primarily employed to treat urinary infections (Figure 32.1). It seems likely that the size of this class of antibiotics will increase due to its wide antibacterial spectrum, favorable pharmacokinetic properties and relative lack of adverse reactions. Unfortunately, their overuse has already led to the emergence of resistant strains resulting in limitations to their clinical usefulness. 

The breakthrough in the development of quinolones came with the appearance of norfloxacin 6 [19], a second-generation quinolone which combined a 6-fluorine substituent with a piperazine ring in the 7-position of the basic compound. Additional quinolones then followed in rapid succession pefloxacin [20], enoxacin [21] and fleroxacin [22] (Fig. 14.5). Particular mention must be made of ciprofloxacin 8 [23-25], ofloxacin 5 [26,27] and its active enantiomer levofloxacin 7 [28]. These quinolones have a broad spectrum of activity, which also includes Gram-positive bacteria and Pseudomonas aeruginosa, as well as favorable pharmacokinetics. The rapid absorption of these compounds from the gastrointestinal tract and their effective tissue penetration also allows them to be used for the treatment of systemic infections. 

A possible pharmacokinetic interaction between ciprofloxacin, which inhibits CYP1A2, and clozapine, with moderately increased serum concentrations of clozapine, has been reported (249). 

Figure 25-6 Conjunctival pharmacokinetics of topical antibodies. (From Wagner RS, Abelson MB, Shapiro A, TorkUdsen G. Evaluation of moxifloxacin, ciprofloxacin, gatifloxacin, ofloxacin, and levofloxacin concentrations in human conjunctival tissue. Arch Ophthalmol 2005 123 1282-1283.)...

Davies SP, Azadian BS, Kox WJ, Brown EA. Pharmacokinetics of ciprofloxacin and vancomycin in patients with acute renal failure treated by continuous haemodialysis. Nephrol Dial Transplant 1992 7 848-54. 

Singlas E, Taburet AM, Landru I, Albin H, Ryckelinck JP. Pharmacokinetics of ciprofloxacin tablets in renal failure influence of haemodialysis. Eur J Clin Pharmacol 1987 31 589-93. 

Pharmacokinetic interaction the drugs interact remotely from the target site to alter plasma (and other tissue) concentrations so that the amount of the drug at the target site of clinical effect is altered, e.g. enzyme induction by rifampicin will reduce the plasma concentration of warfarin enzyme inhibition by ciprofloxacin will elevate the concentration of theophylline. 

Xie, H. Broberg, U. Griskevicius, L. Lundgren, S. Carlens, S. Meurling, L. Paul, C. Rane, A. Hassan, M. Alteration of pharmacokinetics of cyclophosphamide and suppression of the cytochrome p450 genes by ciprofloxacin. Bone Marrow Transplant. 2003, 31, 197-203. 

Forrest, A. Sallow, C.H. Nix, D.E. Birmingham, M.C. Schentag, J.J. Development of a population pharmacokinetic model and optimal sampling strategy for intravenous ciprofloxacin in seriously ill patients. Antimicrob. Agents Chemother. 1993, 57, 1065-1072. 

The pharmacokinetics of intravenous ciprofloxacin have been studied in intensive care unit patients during continuous venovenous hemofiltration (n — 5) or hemo-diafiltration (n — 5) (67). Ciprofloxacin clearance was not altered. A dosage of 400 mg/day was sufficient to maintain effective drug plasma concentrations in patients undergoing continuous renal replacement therapy. 

Some antibiotics can reduce the efficacy of oral contraceptives. However, there is pharmacokinetic evidence that plasma concentrations of oral contraceptive steroids are unchanged by co-administration of ciprofloxacin (75). Furthermore, ciprofloxacin (500 mg bd) did not interfere with the ovarian suppression produced by the oral contraceptive Marvelon (30 micrograms of ethiny-lestradiol plus 150 micrograms of desogestrel) in 24 healthy women in a randomized, double-blind, placebo-controlled, crossover trial (76). 

Malone RS, Fish DN, Abraham E, Teitelbaum I. Pharmacokinetics of levofloxacin and ciprofloxacin during continuous renal replacement therapy in critically iU patients. Antimicrob Agents Chemother 2001 45(10) 2949-54. 

Israel DS, Stotka J, Rock W, Sintek CD, Kamada AK, Klein C, Swaim WR, Pluhar RE, Toscano JP, Lettieri JT, Heller AH, Polk RE. Effect of ciprofloxacin on the pharmacokinetics and pharmacodynamics of warfarin. Clin Infect Dis 1996 22(2) 251-6. 

In 24 healthy volunteers, 12 men and 12 women, the women had significantly different caffeine pharmacokinetics in the presence of ciprofloxacin and fleroxacin compared with the men (132). There were also significant differences between the sexes in the pharmacokinetics of ciprofloxacin and fleroxacin in the presence of caffeine. The differences were in part due to different body weights. 

Co-administration of fenbufen and fluoroquinolones has been associated with seizures (141). The structure at the 7-position greatly affects the risk of NSAID-potentiated nervous system effects. Fluoroquinolones with unsubstituted piperazinyl rings (ciprofloxacin, enox-acin, and norfloxacin) have a strong interaction with NSAIDs (142). The increased risk of seizures is not caused by increased serum concentrations of fluoroquinolones, since their pharmacokinetics are not altered by NSAIDs (143). The mechanism has been suggested to be facilitation by fenbufen of the fluoroquinolone-induced inhibition of GABAa receptor function in the hippocampus and frontal cortex (144). 

Kim MK, Nightingale C, Nicolau D. Influence of sex on the pharmacokinetic interaction of fleroxacin and ciprofloxacin with caffeine. Clin Pharmacokinet 2003 42(ll) 985-96. 

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