Pharmacokinetic profiles of ciprofloxacin after single intravenous and oral doses

supporting

confidence: 79%

Comparative serum bactericidal activities of three doses of ciprofloxacin administered intravenously

Dan

Poch

Quassem

et al. 1994

“…The pharmacokinetic parameters for both drugs appear in (20,25,33,34,46). In contrast, ofloxacin absorption was significantly less affected by Ensure coadministration than ciprofloxacin (P = 0.0016).…”

Section: Resultsmentioning

confidence: 98%

Effect of enteral feeding with ensure on oral bioavailabilities of ofloxacin and ciprofloxacin

Mueller

Brierton

Abel

et al. 1994

The relative oral bioavailabilities of ciprofloxacin and ofloxacin when they were coadministered with water or an enteral feeding product (Ensure) were assessed in 13 healthy volunteers. The area under the concentration time curve from time zero to infinity and the maximum concentration of drug in serum for both drugs were reduced by Ensure in comparison with those by water (P < 0.01). However, Ensure reduced the percent relative bioavailability of ciprofloxacin (72% ± 14%; range, 52 to 96%) significantly more than ofloxacin (90% ± 8.3%; range, 74 to 105%) (P < 0.005). Coadministration of Ensure significantly diminished ciprofloxacin and ofloxacin absorption, but ciprofloxacin absorption was reduced significantly more than ofloxacin absorption.Fluoroquinolone antibiotics represent an important therapeutic advance in the treatment of bacterial infections. The beneficial characteristics of these agents include unique spectra of antimicrobial activity, favorable side effect profiles, and the advantages of both oral and parenteral routes of administration. Many serious infections which previously could be treated only with parenteral drugs can now be treated with an oral fluoroquinolone. The availability of oral fluoroquinolones has allowed more patients to be treated as outpatients and has expanded the use of oral antibiotics to the nursing home and critical care setting (49) to reduce drug costs (12,31,37).The oral bioavailabilities of fluoroquinolone antibiotics may be affected adversely by interactions with divalent cations (1,22,35,39,41). Divalent cations contribute to the clinically important interactions of fluoroquinolone antibiotics with food (9,15,16,18,19,27,42,43,45), vitamins with iron (4, 17, 36), antacids (8,14,21,28,40,41), and sucralfate (10,32,44). Of the two most studied fluoroquinolones, ciprofloxacin absorption appears to be affected more than ofloxacin absorption (6,15,26).The reduced bioavailabilities of oral fluoroquinolone antibiotics because of drug interactions may be important, particularly in the critical care setting, because therapeutic failures have been reported (30,38). The practice of using the enteral rather than the parenteral route to provide nutrition is becoming more common in intensive care units (ICUs) Because of the increasingly common practices of using oral fluoroquinolones and enteral feedings in ICU and nursing home settings, many patients may receive both of these therapies concurrently (23). We conducted a study to assess the influence that concomitant enteral feeding with an enteral feeding product (Ensure) has on the absorption of oral ciprofloxacin and ofloxacin. MATERIALS AND METHODSProtocol. Thirteen healthy adults gave informed consent and were enrolled in the study. Subjects were excluded if they were pregnant or were intending to become pregnant within 30 days of the conclusion of the study. Other exclusion criteria included breastfeeding at the time of the study and use of any medications during the 24 h prior to the study periods. Any known allergies to t...

“…These simulations were designed to achieve total drug concentrations in the central and peripheral compartments that mimicked profiles observed in the serum and skin blister fluid of healthy adults over time (10,32,52). Three experimental dosage simulations were also examined.…”

Section: Methodsmentioning

confidence: 99%

Evolution of Ciprofloxacin-Resistant Staphylococcus aureus in In Vitro Pharmacokinetic Environments

Campion¹,

Evans²

2004

The development of novel antibacterial agents is decreasing despite increasing resistance to presently available agents among common pathogens. Insights into relationships between pharmacodynamics and resistance may provide ways to optimize the use of existing agents. The evolution of resistance was examined in two ciprofloxacin-susceptible Staphylococcus aureus strains exposed to in vitro-simulated clinical and experimental ciprofloxacin pharmacokinetic profiles for 96 h. As the average steady-state concentration (C avg ss ) increased, the rate of killing approached a maximum, and the rate of regrowth decreased. The enrichment of subpopulations with mutations in grlA and low-level ciprofloxacin resistance also varied depending on the pharmacokinetic environment. A regimen producing values for C avg ss slightly above the MIC selected resistant variants with grlA mutations that did not evolve to higher levels of resistance. Clinical regimens which provided values for C avg ss intermediate to the MIC and mutant prevention concentration (MPC) resulted in the emergence of subpopulations with gyrA mutations and higher levels of resistance. A regimen producing values for C avg ss close to the MPC selected grlA mutants, but the appearance of subpopulations with higher levels of resistance was diminished. A regimen designed to maintain ciprofloxacin concentrations entirely above the MPC appeared to eradicate low-level resistant variants in the inoculum and prevent the emergence of higher levels of resistance. There was no relationship between the time that ciprofloxacin concentrations remained between the MIC and the MPC and the degree of resistance or the presence or type of ciprofloxacin-resistance mutations that appeared in grlA or gyrA. Regimens designed to eradicate low-level resistant variants in S. aureus populations may prevent the emergence of higher levels of fluoroquinolone resistance.