Serum Concentrations Of Ciprofloxacin Research Articles

Ciprofloxacin Inhibition of Experimental Fracture-Healing*

Fluoroquinolones, such as ciprofloxacin, have an adverse effect on growing cartilage and endochondral ossification in children. This study was carried out to determine whether ciprofloxacin also has an adverse effect on the healing of experimental fractures. Sixty male 300-gram Wistar rats were divided equally into three groups, which received ciprofloxacin, cefazolin, or no treatment for three weeks, beginning seven days after production of a closed, nondisplaced, bilateral femoral fracture. The serum concentrations of the ciprofloxacin and the cefazolin were 2.4 and 146 micrograms per milliliter, respectively. Radiographic, histological, and biomechanical studies were used to evaluate fracture-healing. Radiographs revealed significantly more advanced healing of the control fractures compared with the fractures in the ciprofloxacin-treated group (average stage, 2.1 compared with 1.5, p = 0.01). The cefazolin-treated group was not different from the controls with respect to radiographic healing (average stage, 1.8 compared with 2.1, p = 0.18). Torsional strength-testing of fracture callus exposed to ciprofloxacin revealed a 16 percent decrease in strength compared with the controls (284 compared with 338 newton-millimeters, p = 0.04) and a 49 percent decrease in stiffness (twenty compared with thirty-nine newton-millimeters per degree, p = 0.001). The biomechanical strength in the cefazolin-treated group was not different from that of the controls. Fracture calluses in the animals treated with ciprofloxacin showed abnormalities in cartilage morphology and endochondral bone formation and a significant decrease in the number of chondrocytes compared with the controls (0.77 x 10(4) compared with 1.3 x 10(4) cells per square millimeter, p = 0.004). These data suggest that experimental fractures exposed to therapeutic concentrations of ciprofloxacin in serum demonstrate diminished healing during the early stages of fracture repair. The administration of ciprofloxacin during early fracture repair may compromise the clinical course of fracture-healing.

Ciprofloxacin concentrations in lung tissue following a single 400 mg intravenous dose.

Intravenous ciprofloxacin is frequently prescribed for the treatment of infections due to nosocomially acquired gram-negative organisms, including those originating in the respiratory tract. In this study, the concentrations of ciprofloxacin in serum and lung tissue were determined by HPLC in patients undergoing lung surgery. A total of 22 patients scheduled for lung surgery received a single 400 mg i.v. dose of ciprofloxacin administered as a 1 h infusion. A specimen of healthy lung tissue was obtained from resected lung from 18 of the patients for analysis of ciprofloxacin concentration during the following time intervals after infusion (one sample/patient): 0-2, 2-4, 4-8 and 8-12 h. Corresponding mean serum and tissue concentrations were 2.37 mg/L and 3.84 mg/kg (0-2 h), 1.18 mg/L and 1.92 mg/kg (2-4 h), 0.69 mg/L and 1.77 mg/kg (4-8 h), and 0.13 mg/L and 0.67 mg/kg (8-12 h). Ciprofloxacin distributed rapidly to lung tissue, as seen by the high concentrations in the lung tissue as early as 2 h after infusion. Concentrations in lung tissue were generally higher than those in serum (tissue:serum ratios ranged from 1.7 to 7.1). The mean tissue concentrations found in this study remained above the MIC for most susceptible organisms.

Sequential intravenous-oral ciprofloxacin plus amoxycillin/clavulanic acid shortens hospital stay in infected non severe neutropenic patients.

The objective of this study was to determine the efficacy and safety of the combination ciprofloxacin plus amoxicillin/clavulanic acid as an empirical treatment of infection in hematologic patients without severe neutropenia. These drugs allowed us to carry out a sequential therapy, first intravenously and later orally, so that the patient could be discharged as soon as there was a response. Serum concentrations of ciprofloxacin were monitored in this study. Forty seven of the sixty-six patients included (71%) responded to the treatment with no differences between the dosages of ciprofloxacin employed (600-900 mg daily in two or three divided doses). In the patients who responded, the signs and symptoms of infection lasted only three days, which could allow a short hospital stay (median of six days). In the first pre and post-dose serum samples, ciprofloxacin concentrations were significantly higher when the drug was administered every 8 h. Nevertheless, 72 h after the beginning of treatment, they had leveled out in either 8 and 12 h schemes. The toxicity of the treatment was very light, with only four cases with adverse effects, grades I and II. This data suggests that the employed combination is effective and safe and can considerably decrease costs incurred through the admission of hematologic patients with serious infections but without severe neutropenia.

Effect of ciprofloxacin on the hypoprothrombinemic activity of warfarin in rats

The interaction between the fluoroquinolone ciprofloxacin and the oral anticoagulant warfarin was investigated in male Wistar rats in two phases. In phase I, the optimum oral dose of warfarin was determined to be 0.1 mg/kg in rats. This dose prolonged the prothrombin time (PT) 1.5–2 times the control values. On phase II, for a period of 5 consecutive days, three groups of animals received daily oral doses of one of the following treatments: warfarin sodium 0.1 mg/kg (group I), ciprofloxacin 20 mg/kg (group II), or a combination of ciprofloxacin and warfarin (group III). PT was determined for all animals before and after each treatment. Ciprofloxacin serum concentrations were measured using an HPLC assay. The mean PT before treatment was 12.3 ± 2.8 seconds. One hour after the last treatment in the three groups, the PT of the combination group was significantly higher than that of both of the warfarin and the ciprofloxacin groups (32.7 ±10 vs. 18.9 ± 5.2 and 14.4 ±0.9 seconds, respectively). Whereas, 3 days after the last treatment, the PTs were found to be 15.8 ± 1.1, 18.6 ±0.7 and 14.6 ± 2 seconds for the combination, warfarin and ciprofloxacin groups, respectively. Interestingly, animals in group three seemed to recover more rapidly and fully on day 8. The results indicate that this interaction is serious and could be fatal if not monitored, however it is reversible if ciprofloxacin is discontinued.

Ciprofloxacin absorption is impaired in patients given enteral feedings orally and via gastrostomy and jejunostomy tubes

Twenty-six hospitalized patients participated in a randomized crossover study to evaluate the effect of enteral feedings on ciprofloxacin absorption when given orally or via gastrostomy or jejunostomy tubes. Patients in the oral group received an intact 500-mg ciprofloxacin tablet alone or ciprofloxacin plus three oral doses of Sustacal (240 ml given 8 h before, with, and 4 h after ciprofloxacin administration). Patients with gastrostomy or jejunostomy tubes received 500 mg of crushed ciprofloxacin in 60 ml water via the feeding tube. After a washout period, the patients received ciprofloxacin with a continuous enteral formula (Jevity) given at 60 to 90 ml/h beginning 6 h before drug administration and continuing for 10 h. Serial blood samples were analyzed for ciprofloxacin concentration by high-performance liquid chromatography. The maximum ciprofloxacin concentrations in serum for ciprofloxacin given and for ciprofloxacin plus enteral feeding for the oral, gastrostomy, and jejunostomy groups were (mean +/- standard deviation) 2.59 +/- 1.24 versus 1.43 +/- 0.61 micrograms/ml (P < 0.05), 3.68 +/- 1.36 versus 2.27 +/- 0.67 micrograms/ml (P < 0.05), and 3.78 +/- 1.87 versus 1.45 +/- 0.48 micrograms/ml (P < 0.05), respectively. Corresponding values for area under the concentration-time curve were 13.4 +/- 8.32 versus 9.44 +/- 4.74 micrograms/h/ml (P < 0.05) 15.9 +/- 6.62 versus 7.44 +/- 3.16 (micrograms/h/ml (P < 0.05), and 18.1 +/- 9.37 versus 5.82 +/- 2.63 micrograms.h/ml (P < 0.05). We conclude that enteral feedings given orally or via gastrostomy or jejunostomy tubes resulted in a 27 to 67% reduction in the mean bioavailability of ciprofloxacin in hospitalized patients. The decreased absorption may be clinically important, especially when the enteral feeding is coadministered with ciprofloxacin by the oral and jejunostomy tube routes. Reductions in maximum levels of ciprofloxacin in serum as a result of feedings given via a gastrostomy tube are similar to those following oral administration on an empty stomach, making a clinically important interaction by this route less likely.

シプロフロキサシンの消化管吸収に及ぼすクエン酸第一鉄ナトリウムの影響

The effect of sodium ferrous citrate (SFC) on the relative bioavailability of ciprofloxacin (CPFX) after a single 600-mg oral dose of CPFX was studied in three healthy volunteers. Blood samples were collected at regular intervals 0-8 h post-dose. CPFX concentrations in serum were determined by bioassay method. The area under the serum concentration-time curve (AUC) decreased significantly (p<0.05) after CPFX was taken with 100 mg SFC. The relative bioavailability was 33.1±15.0% when CPFX was given with SFC. The maximum blood level decreased from 3.96±1.30 (control) to 1.36±1.00μg/ml (with SFC). The mechanism of the CPFX-iron ion interaction appears to be the formation of chelation complex.Ascorbic acid is known to interfere with the formation of chelation complex. Therefore, the effect of SFC on the absorption of CPFX with concomitant administration of 1500 mg ascorbic acid was studied in two healthy volunteers using the same method. The AUC increased from 4.37 and 3.50 (with SFC) to 5.23 and 5.39μg·hr/ml (with SFC and ascorbic acid). However, the relative bioavailability was 33.3 and 27.7% when CPFX was taken alone. Ascorbic acid did not appear to interfere much with the formation of CPFX-iron ion chelation complex.

Reduction in Serum Concentrations of Ciprofloxacin After Administration of Ursodiol to a Patient with Hepatobiliary Disease

Journal Article Reduction in Serum Concentrations of Ciprofloxacin After Administration of Ursodiol to a Patient with Hepatobiliary Disease Get access Paul P. Belliveau, Paul P. Belliveau Department of Pharmacy and Division of lnfectious Diseases and Allergy/Immunology, Hartford Hospital, Hartford; the School of Pharmacy, University of Connecticut, Storrs; and the School of Medicine, University of Connecticut, Farmington, Connecticut Reprints or correspondence: Dr. Paul P. Belliveau, Department of Pharmacy, University of Massachusetts Medical Center, 55 Lake Avenue North, Worcester, Massachusetts 06115. Search for other works by this author on: Oxford Academic PubMed Google Scholar Charles H. Nightingale, Charles H. Nightingale Department of Pharmacy and Division of lnfectious Diseases and Allergy/Immunology, Hartford Hospital, Hartford; the School of Pharmacy, University of Connecticut, Storrs; and the School of Medicine, University of Connecticut, Farmington, Connecticut Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard Quintiliani, Richard Quintiliani Department of Pharmacy and Division of lnfectious Diseases and Allergy/Immunology, Hartford Hospital, Hartford; the School of Pharmacy, University of Connecticut, Storrs; and the School of Medicine, University of Connecticut, Farmington, Connecticut Search for other works by this author on: Oxford Academic PubMed Google Scholar Eufronio G. Maderazo Eufronio G. Maderazo Department of Pharmacy and Division of lnfectious Diseases and Allergy/Immunology, Hartford Hospital, Hartford; the School of Pharmacy, University of Connecticut, Storrs; and the School of Medicine, University of Connecticut, Farmington, Connecticut Search for other works by this author on: Oxford Academic PubMed Google Scholar Clinical Infectious Diseases, Volume 19, Issue 2, August 1994, Pages 354–355, https://doi.org/10.1093/clinids/19.2.354 Published: 01 August 1994

Serum ciprofloxacin concentrations in patients with severe sepsis being treated with ciprofloxacin 200 mg i.v. bd irrespective of renal function.

Serum ciprofloxacin concentrations in patients with severe sepsis being treated with ciprofloxacin 200 mg i.v. bd irrespective of renal function.

Prevalence of Helicobacter pylori in gastrointestinal disorders and concentrations of ciprofloxacin in serum and gastric mucosa

Endoscopic antral biopsies were obtained from 30 patients with several gastrointestinal disorders and analysed for the presence of H. pylori. This bacterium was present in 80% and 58%, respectively, of patients with either gastric and duodenal ulcers and gastric neoplasm. In none of the healthy individuals, H. pylori could be found. Another 14 patients with various diseases of the stomach, undergoing a major gastric resection, had been treated with 200 mg ciprofloxacin intravenously immediately before the operation. Blood and various tissues samples were taken during the operation. The prevalence of IgG antibodies against H. pylori in these patients was 93%. H. pylori could be determined in 71% of the cases by the urease production; by culture, this was possible in only one case. The mean peak concentration of ciprofloxacin in serum was 5.31 mg/l and 1.17 mg/l, respectively, immediately and 60 min after the end of infusion; in tissues of antrum and duodenum, 1.59 to 1.64 mg/kg and 1.41 to 1.72 mg/kg, respectively, 45-270 min after the infusion. The results show that ciprofloxacin rapidly penetrates into tissues and attains concentrations greater than the MIC90 for H. pylori. However, these concentrations can inhibit the isolation of this microorganism but not its urease activity. This fact could be interpreted by the existence of a nonculturable but metabolically active form of H. pylori. This would explain the high rate of recrudescence following most types of currently applied therapeutic schemes.

The penetration of ciprofloxacin into bronchial mucosa, lung parenchyma, and pleural tissue after intravenous administration

We have studied the concentrations of ciprofloxacin in serum, bronchial mucosa, lung parenchyma, and pleural tissue after a single intravenous dose of 200 mg in 20 patients subjected to lung surgery. The concentrations of ciprofloxacin in the tissues exceeded that in the serum by 3-fold to 7-fold: serum 0.6 micrograms.ml-1, bronchial mucosa 1.9 micrograms.g-1, lung parenchyma 3.4 micrograms.g-, and pleural tissue 1.7 micrograms.g-1. The achievable concentrations of ciprofloxacin in the tissues of the lower respiratory tract are above the MICs for most lung pathogens.

Pharmacokinetics of Ciprofloxacin after Single Oral and Intravenous Doses

Intravenous ciprofloxacin had previously been approved in the United States at doses up to 200mg every 12 hours. Bioavailability data suggested that higher intravenous doses would be needed to achieve the same serum concentrations as attained by the standard oral doses of 500 and 750mg. This study directly compared ciprofloxacin serum concentrations after single oral doses of 500 and 750mg with those after single intravenous doses of 300 and 400mg. The aims of the study were 2-fold: a) to determine the bioequivalence relationships between intravenous ciprofloxacin (300 and 400mg) and oral ciprofloxacin (500 and 750mg); and b) to assess the comparative safety and tolerability of single doses of intravenous and oral ciprofloxacin. This was a randomised double-blind 4-period crossover study in 12 healthy male volunteers, aged 18 to 40 years. Treatments consisted of single doses of a) ciprofloxacin 300mg infused over 60 minutes; b) ciprofloxacin 400mg infused over 60 minutes; c) oral ciprofloxacin 500mg (as 2 X 250mg tablets); and d) oral ciprofloxacin 750mg (as 3 X 250mg tablets). Matching placebo tablets or infusion of normal saline were incorporated to maintain the double-blind nature of the trial. There was a I-week washout between each dose. Serum samples for ciprofloxacin assay were obtained before each dose, at 15 and 30 minutes into the infusion (drug or placebo), and at 0.25, 0.5, 1,2,3,4,5, 7, 9, II, 15, 19, and 23 hours after the end of infusion. Urine was collected over intervals of 0 to 12 hours and 12 to 24 hours. Concentrations of ciprofloxacin were determined by a fully validated HPLC procedure, with a sensitivity of 0.02 mg/L, precision of greater than 95%, and accuracy greater than 90%. Area under the curve (AUC) from 0 to 24 hours was calculated by applying the log trapezoidal rule. Extrapolation to infinity was accomplished by adding the value 1.44t'/2Cn to AUCO-24, where Cn is the predicted concentration at 24 hours based on linear regression of the terminal slope of the log concentration vs time curve. Half-life (t'/2) was calculated as 0.693/s10pe. At least 4 data points were used in each tl/z determination. Maximum serum concentration (Cmax) was obtained from the observed data. Renal clearance (CLR) was calculated as amount excreted/AUC. Primary analysis included only 11 subjects, since 1 subject had aberrant serum values after the 300mg infusion. Inclusion of this subject's data did not alter any of the conclusions of this report. Statistical analysis consisted of analysis of variance with pairwise comparisons of least squares means of pharmacokinetic variables for different doses with or without

Interaction between ciprofloxacin and thiopental in the central nervous system of the male rat.

The effect of intravenous ciprofloxacin (CPX) pretreatment on the kinetics and brain sensitivity for thiopental was studied in male rats using a previously developed electroencephalographic (EEG) threshold method. Thiopental was administered intravenously with constant infusion rate. Immediately after the appearance of the first burst suppression of 1 sec. or more (the "silent-second") in the EEG the infusion was stopped and the rats were killed by decapitation. The dose of thiopental needed to reach the criterion of silent-second was slightly reduced in ciprofloxacin pretreated rats when compared with saline pretreated controls. One rat that developed seizures after CPX pretreatment needed a considerably reduced dose of thiopental to induce the silent-second. The serum concentrations of thiopental were markedly reduced in the experimental group while no significant differences were found in the concentrations of thiopental in the different parts of the central nervous system (CNS), fat or muscle tissue. The kinetics of CPX were also affected. The experimental group (CPX + thiopental treated) had significant higher brain concentrations of CPX than the corresponding only CPX treated control group while no differences were found in the serum concentrations of CPX between the groups. As previously suggested, the distribution of thiopental in the CNS is not only dependent on its lipid solubility, but also as a weak organic acid, on the transport system for organic acids out of the CNS which both thiopental and ciprofloxacin seem to use and mutually compete for it.

Use of ciprofloxacin versus use of aminoglycosides for therapy of complicated urinary tract infection: prospective, randomized clinical and pharmacokinetic study

The efficacy of oral ciprofloxacin was compared with that of parenteral aminoglycoside for therapy of complicated urinary tract infection in a prospective randomized trial. The setting was a chronic-care Veterans Administration facility in which long-term bladder catheterization and resistant bacteria were common. Sixty-five consecutive patients were stratified for presence and type of bladder catheter, the presence of Providencia and Pseudomonas aeruginosa organisms versus other urinary pathogens, and renal dysfunction. A pharmacokinetic study of ciprofloxacin concentrations in serum and urine was performed with selected patients. Urinary catheters were present in 94%. All patients were symptomatic, and 58.5% had fever. Ciprofloxacin, 500 mg every 12 h orally, was compared with parenteral aminoglycoside for 7 to 10 days. Clinical response, defined by resolution of symptoms and fever at 5 to 9 days posttherapy (short-term) and 28 to 30 days posttherapy (long-term), was essentially identical for both treatment groups. Bacteriologic response, defined by sterile urine cultures, showed that ciprofloxacin was significantly more efficacious (P = 0.0005) than aminoglycoside at 5 to 9 days posttherapy. However, by 28 to 30 days, the response rate was essentially identical. Emergence of resistance to the study antibiotic was seen in 62 and 70% of those who did not show a bacteriological response and were receiving ciprofloxacin and aminoglycosides, respectively. Concentrations of ciprofloxacin and aminoglycoside in the urine substantially exceeded the MIC for the urinary pathogens isolated, although these concentrations did not correlate with short-term bacteriologic response for either antibiotic. Ciprofloxacin was efficacious in complicated urinary tract infection compared with the current standard of parenteral aminoglycoside among catheterized patients with relatively resistant bacteria.

Ciprofloxacin in patients with mycobacterial infections: experience in 15 patients.

In vitro and animal investigations have demonstrated the antimycobacterial activity of some fluoroquinolones, including ciprofloxacin, but information regarding their clinical usefulness in mycobacterial infections is sparse. This article presents treatment results of 11 patients with tuberculosis and 4 with atypical mycobacterial infections. They were treated with combinations of ciprofloxacin and one or two other antituberculosis agents. Susceptibility of the infecting organisms to ciprofloxacin was determined in 14 of the 15 patients: in 12 of them, minimum inhibitory concentrations ranged between 0.31 and 1.25 micrograms/mL, suggesting a good level of activity. Serum concentrations of ciprofloxacin, sampled one hour after dosing and measured by a specific HPLC assay, revealed considerable variability (range 0.22-8.41 micrograms/mL). Serial plasma samples taken under controlled conditions suggested that a decreased rate of absorption was responsible for low one-hour concentrations in one of the subjects. Adverse reactions to ciprofloxacin were few and included nausea in four patients, crystalluria in one, and febrile reaction in another. A satisfactory response in terms of clinical and radiologic improvement, bacteriologic conversion, and absence of relapse was seen in 13 of the 14 patients who completed an adequate course of therapy. A controlled clinical trial of this promising antimycobacterial agent is needed.

Clinical and chemical interactions between iron preparations and ciprofloxacin.

1. The effect of ferrous sulphate (300 mg), ferrous gluconate (600 mg), and a combination tablet of iron (10 mg), magnesium (100 mg), zinc (15 mg), calcium (162 mg), copper (2 mg), and manganese (5 mg) (Centrum Forte) co-administration on ciprofloxacin bioavailability was tested in eight healthy subjects. 2. Peak serum ciprofloxacin concentrations and area under the curve (AUC) were significantly reduced when ciprofloxacin was administered with 300 mg ferrous sulphate (3.0 vs 2.0 mg l-1, P less than 0.05 and 12.3 vs 6.7 mg l-1 h, P less than 0.01, respectively). Reductions in peak ciprofloxacin concentrations and AUC also occurred when ciprofloxacin was ingested with 600 mg ferrous gluconate (1.3 mg l-1, P less than 0.01 and 4.1 mg l-1 h, P less than 0.01, respectively) and a Centrum Forte tablet (1.4 mg l-1, P less than 0.01 and 5.4 mg l-1 h, P less than 0.01, respectively). 3. When ferrous ion was mixed with ciprofloxacin, rapid spectral changes occurred (t1/2 = 1.9 min). Additional studies were consistent with oxidation of the ferrous form of iron to its ferric form, which is followed by rapid formation of a Fe(3+)-ciprofloxacin complex. Ciprofloxacin seems to bind to ferric ion in a ratio of 3:1 by interacting with the 4-keto and 3-carboxyl groups on ciprofloxacin. 4. The formation of a ferric ion-ciprofloxacin complex is probably the cause of the reduction in ciprofloxacin bioavailability in the presence of iron.

Influence of subject age on the inhibition of oxidative metabolism by ciprofloxacin

Case reports suggest that the magnitude of inhibition of oxidative metabolism produced by ciprofloxacin may be greater in elderly subjects. We examined the effect of oral ciprofloxacin on antipyrine disposition in 13 young (ages, 23 to 34 years) and 9 elderly (ages, 65 to 82 years) healthy volunteers. Ciprofloxacin decreased antipyrine oral clearance in young and elderly subjects (P less than 0.05), with the average decreases being similar in both groups (23.3% for the young subjects and 27.9% for the elderly subjects). Ciprofloxacin concentrations in serum were significantly higher (mean, 57%) in the elderly. The formation clearance of 4-hydroxyantipyrine and 3-hydroxymethylantipyrine was also significantly decreased in both groups of subjects; however, norantipyrine formation, accounting for 15 to 20% of antipyrine clearance, was reduced only in the elderly. These results suggest that elderly subjects are not more sensitive to the inhibitory effect of ciprofloxacin on antipyrine metabolism. However, careful clinical monitoring is necessary with all patients, irrespective of age, taking ciprofloxacin concomitantly with drugs primarily eliminated by the cytochrome P-450 system.

Clinical Pharmacokinetics of Ciprofloxacin

Compared with nalidixic acid, ciprofloxacin is representative of a newer, more potent class of quinolones, termed the fluoroquinolones. It is available in both oral and parenteral dosage forms. The primary target of quinolone activity appears to be the bacterial DNA gyrase enzyme, which is a member of the class of type II topoisomerases. Bacterial do not acquire resistance to fluoroquinolones through mechanisms that are plasmid or R-factor mediated and, additionally, the quinolones do not appear to be vulnerable to degradation by bacterial inactivating mechanisms. Rather, bacterial resistance to ciprofloxacin occurs either through chromosomal mutation in the target enzyme DNA gyrase or through mutations that alter drug permeability into the bacterial cell. Ciprofloxacin and the fluoroquinolones in general are no more likely to select resistant mutant than are aminoglycosides or beta-lactam antibiotics. Ciprofloxacin displays in vitro activity against most Gram-negative and many Gram-positive pathogenic bacteria, many of which are resistant to a wide range of antibiotics. This finding is of considerable potential clinical significance. High pressure liquid chromatography (HPLC) and microbiological agar diffusion assays have been routinely used to quantify ciprofloxacin concentrations in biological fluids. Both methods are reproducible and accurate for serum but HPLC is recommended for other specimens because of the presence of microbiologically active metabolites. Absorption after oral administration is rapid and can be satisfactorily described as a zero-order process; peak serum ciprofloxacin concentrations (Cmax) are reached in approximately 1 to 2 hours. Concomitant administration of food does not cause clinically significant impairment of absorption and may be helpful in minimising gastric distress caused by the drug. A linear relationship between serum ciprofloxacin concentrations and the dose administered either orally or intravenously has been reported. The absolute bioavailability of ciprofloxacin is approximately 70%. The volume of distribution is large with a steady-state range after oral or intravenous dosing of 1.74 to 5.0 L/kg reflecting penetration of the drug into most tissues. Nonrenal clearance accounts for approximately 33% of the elimination of ciprofloxacin; to date, 4 metabolites have been identified. A first-pass effect has been reported but is thought to be clinically unimportant. Faecal recovery of ciprofloxacin accounts for approximately 15% of an intravenous dose. Nonrenal elimination includes metabolic degradation, biliary excretion and transluminal secretion across the enteric mucosa. Glomerular filtration and tubular secretion account for approximately 66% of the total serum clearance. The terminal disposition half-life (t1/2) is about 3 to 4 hours.(ABSTRACT TRUNCATED AT 400 WORDS)

Decreased ciprofloxacin absorption with concomitant administration of ferrous fumarate

The effect of ferrous fumarate on the relative bioavailability of ciprofloxacin after a single 500 mg oral dose of ciprofloxacin was studied in eight healthy males. Blood samples were collected at regular intervals 0-24 h post-dose. Urine was collected during 24 h to determine the cumulative urine excretion of ciprofloxacin. Ciprofloxacin concentrations in serum and urine were determined by high pressure liquid chromatography. Mean area under the serum concentration-time curve decreased significantly (P less than 0.001) after ciprofloxacin was taken with 200 mg ferrous fumarate. The relative bioavailability was 30% when ciprofloxacin was given with ferrous fumarate. The maximum blood level decreased from 2.1 +/- 0.9 (control) to 0.6 +/- 0.2 mg/l (with ferrous fumarate). Further studies are needed to determine if chronic treatment with ferrous fumarate further decreases the relative bioavailability. For the moment administration of ciprofloxacin with ferrous fumarate should therefore be avoided.

Alteration in the pharmacokinetic disposition of ciprofloxacin by simultaneous administration of azlocillin

Healthy subjects were given single intravenous doses of ciprofloxacin, azlocillin, and the two drugs simultaneously on separate occasions. High-pressure liquid chromatographic analysis was used to assay the concentrations of both drugs in serum and urine. Pharmacokinetic parameters were calculated by noncompartmental methods. The total body (CL), renal (CLR), and nonrenal (CLNR) clearances; steady-state volume of distribution (Vss); and fractional urinary excretion of ciprofloxacin were all markedly decreased with the simultaneous administration of azlocillin. The disposition of azlocillin was unchanged when it was given with ciprofloxacin compared to when it was given alone. The pharmacokinetic parameters (mean +/- standard deviation) of ciprofloxacin given alone versus in combination with azlocillin were as follows: CL, 52.2 +/- 9.2 versus 33.9 +/- 6.0 liters/h (P less than 0.0005); CLR, 26.5 +/- 4.8 versus 16.2 +/- 4.2 liters/h (P less than 0.0005); CLNR, 25.8 +/- 5.5 versus 17.7 +/- 4.0 liters/h (P less than 0.03); Vss, 224 +/- 30 versus 166 +/- 41 liters (P less than 0.01); fractional urinary excretion, 0.56 +/- 0.06 versus 0.43 +/- 0.04 (P less than 0.002), respectively. This interaction resulted in significantly higher and more prolonged concentrations of ciprofloxacin in serum, which may be beneficial in the treatment of serious gram-negative bacterial infections, but it could also produce greater toxicity or result in more pronounced effects on oxidative drug metabolism of other medications.

Sucralfate significantly reduces ciprofloxacin concentrations in serum

The effect of sucralfate on the bioavailability of ciprofloxacin was evaluated in eight healthy subjects utilizing a randomized, crossover design. The area under the concentration-time curve from 0 to 12 h was reduced from 8.8 to 1.1 micrograms.h/ml by sucralfate (P less than 0.005). Similarly, the maximum concentration of ciprofloxacin in serum was reduced from 2.0 to 0.2 micrograms/ml (P less than 0.005). We conclude that concurrent ingestion of sucralfate significantly reduces the concentrations in serum produced by a 500-mg dose of ciprofloxacin. On the basis of these findings, ciprofloxacin and sucralfate should not be administered concurrently.