Serum Concentrations Of Ciprofloxacin Research Articles

Compatible co-administration of BioThrax® vaccine and ciprofloxacin—Results of a randomized open-label drug-vaccine interaction trial

The recommended treatment for post-exposure prophylaxis (PEP) following known/suspected exposure to Bacillus anthracis involves immunization with anthrax vaccine adsorbed (AVA, i.e., BioThrax® vaccine) and a course of antimicrobial therapy. A drug-vaccine interaction clinical trial was conducted to determine whether this combined treatment might modify antimicrobial exposure or vaccine immunogenicity.A Phase 2, randomized, open-label, multi-center trial involving 154 healthy adult participants was completed to evaluate the effect of AVA immunization (three doses administered subcutaneously (SC) at weeks 0, 2 and 4) on the pharmacokinetics (PK) of ciprofloxacin, as well as the effect of ciprofloxacin administration (500 mg po bid) on the immunogenicity of AVA. PK parameters were derived using noncompartmental analysis of ciprofloxacin serum concentrations. Immunogenicity was assessed using a toxin neutralizing antibody (TNA) assay resulting in 50 % neutralization factor (NF50) values. Safety was assessed via reports of adverse events (AEs), clinically significant changes in laboratory parameters and vital signs, and collection of solicited local and systemic reactogenicity reactions.Statistical analyses of the steady state (SS) and single dose PK parameters Cmax and AUC0-–12h indicated that the AVA PEP regimen did not significantly modify ciprofloxacin exposure. Comparison of the geometric mean TNA NF50 values between participants receiving AVA + ciprofloxacin and those receiving AVA alone showed that the combined treatment was non-inferior to AVA alone. The trial met all prospectively defined success criteria for the primary PK endpoint and for the secondary PK and immunogenicity endpoints. There were no deaths, SAEs or AEs leading to drug discontinuation or study withdrawal during the trial.Overall, concomitant administration of ciprofloxacin and AVA produced no significant changes in the PK profile of ciprofloxacin nor in the immunogenicity of AVA. Furthermore, this trial demonstrated that the co-administration of ciprofloxacin and AVA was well tolerated in healthy adult participants.

Gene Polymorphism of Biotransformation Enzymes and Ciprofloxacin Pharmacokinetics in Pediatric Patients with Cystic Fibrosis.

(1) Background: Ciprofloxacin (CPF) is widely used for the treatment of cystic fibrosis, including pediatric patients, but its pharmacokinetics is poorly studied in this population. Optimal CPF dosing in pediatric patients may be affected by gene polymorphism of the enzymes involved in its biotransformation. (2) Materials and Methods: a two-center prospective non-randomized study of CPF pharmacokinetics with sequential enrollment of patients (n-33, mean age 9.03 years, male-33.36%), over a period from 2016 to 2021. All patients received tablets of the original CPF drug Cyprobay® at a dose of 16.5 mg/kg to 28.80 mg/kg. Blood sampling schedule: 0 (before taking the drug), 1.5 h; 3.0 h; 4.5 h; 6.0 h; 7.5 h after the first dosing. CPF serum concentrations were analyzed by high performance liquid chromatography mass spectrometry. The genotype of biotransformation enzymes was studied using total DNA isolated from whole blood leukocytes by the standard method. (4) Results: a possible relationship between the CA genotype of the CYP2C9 gene (c.1075A > C), the GG genotype of the CYP2D6*4 gene (1846G > A), the AG genotype of the GSTP1 gene (c.313A > G), the GCLC* genotype 7/7 and the CPF concentration in plasma (increased value of the area under the concentration–time curve) was established. Conclusions: Gene polymorphism of biotransformation enzymes may affect ciprofloxacin pharmacokinetics in children.

Effect of RecA inactivation on quinolone susceptibility and the evolution of resistance in clinical isolates of Escherichia coli.

SOS response suppression (by RecA inactivation) has been postulated as a therapeutic strategy for potentiating antimicrobials against Enterobacterales. To evaluate the impact of RecA inactivation on the reversion and evolution of quinolone resistance using a collection of Escherichia coli clinical isolates. Twenty-three E. coli clinical isolates, including isolates belonging to the high-risk clone ST131, were included. SOS response was suppressed by recA inactivation. Susceptibility to fluoroquinolones was determined by broth microdilution, growth curves and killing curves. Evolution of quinolone resistance was evaluated by mutant frequency and mutant prevention concentration (MPC). RecA inactivation resulted in 2-16-fold reductions in fluoroquinolone MICs and modified EUCAST clinical category for several isolates, including ST131 clone isolates. Growth curves and time-kill curves showed a clear disadvantage (up to 10 log10 cfu/mL after 24 h) for survival in strains with an inactivated SOS system. For recA-deficient mutants, MPC values decreased 4-8-fold, with values below the maximum serum concentration of ciprofloxacin. RecA inactivation led to a decrease in mutant frequency (≥103-fold) compared with isolates with unmodified SOS responses at ciprofloxacin concentrations of 4×MIC and 1 mg/L. These effects were also observed in ST131 clone isolates. While RecA inactivation does not reverse existing resistance, it is a promising strategy for increasing the effectiveness of fluoroquinolones against susceptible clinical isolates, including high-risk clone isolates.

Ciprofloxacin in critically ill subjects: considering hepatic function, age and sex to choose the optimal dose.

Pathophysiological changes often result in altered pharmacokinetics of ciprofloxacin in critically ill patients. Although ciprofloxacin clearance (CLCIP) substantially depends on kidney function in healthy volunteers, its relationship to measured creatinine clearance (CLCRM) is weak in critically ill patients. To assess the need for dose reductions in isolated or combined kidney and liver dysfunction in critically ill patients and to re-evaluate relationships between kidney parameters, demographics and ciprofloxacin pharmacokinetics. A population pharmacokinetic model was developed based on 444 ciprofloxacin serum concentrations from 15 critically ill patients with severe infections. CLCIP relationships to parameters reflecting hepatic function, CLCRM, Cockcroft-Gault creatinine clearance (CLCRCG), serum creatinine, sex, weight and age were explored. A simulation study was conducted to integrate knowledge from the new and previously published models. Total bilirubin was identified as a hepatic parameter with a clear relationship to CLCIP. A significant relationship between CLCIP and CLCRCG could be attributed to age and sex only. CLCIP was not associated with CLCRM. The predicted risk of potential overexposure (AUC > 250 mg·h/L) was low even with 1200 mg/day ciprofloxacin daily for patients with reduced CLCRCG (<30 mL/min: risk of 0.7%), while the risk was remarkably higher in elderly female patients with elevated bilirubin (risk of about 20% for 65-year-old women with total bilirubin of 4 mg/dL). Bilirubin, age and sex should be considered to assess the need for dose reductions. For MICs ≤0.25 mg/L, it might be appropriate to reduce the dose to 400 mg/day for elderly female subjects with high bilirubin.

Pharmacokinetics of ciprofloxacin in bath medicated hybrid tilapias using enzyme linked immunosorbent assay (ELISA)

The apparent absence of established dosage regime for medicating tilapia with fluoroquinolones in the country necessitated investigating the absorption and tissue distribution of ciprofloxacin, since dosage regimes conform to accepted standards of pharmacokinetic studies. Ciprofloxacin pharmacokinetic studies were conducted on 76 hybrid tilapia weighing between 100 and 200 grams divided into two groups with each subjected to bath administration of ciprofloxacin at two different concentrations. The fishes in groups 1 and 2 were exposed by bath to 50 mg and 25 mg respectively of ciprofloxacin per litre of water. Tissue and blood samples were collected at 0.5h, 1h, 2h, 4h, and 8h during medication and drug withdrawal at 24h, 48h, and 72h, to quantify their ciprofloxacins by Enzyme Linked Immunosorbent Assay (ELISA). Peak serum concentration of ciprofloxacin in group 1 was 2,251±877 μg/L at 8 h while for group 2; it was 2,226±174 μg/L at 4 h exposure time. The t- test comparing the means of the groups 1 and 2 showed that there was no significant statistical difference (p > 0.05) on group sera, liver and kidney, except skeletal muscle ciprofloxacin concentration. The elimination half-lives in groups 1 and 2 were determined on serum ciprofloxacin values, after withdrawal of drug and were 27.75 h and 31.8 h, with rate constant of elimination being 0.025 h-1 and 0.022 h-1 respectively. Sera Area under Curve, {AUC (0.5-8h)} values were 12,159.3 and 13,194 μg/L respectively with 92.2% correlation. Prolonged high ciprofloxacin concentration was observed in tilapia skeletal muscle. High correlation in sera AUC values is suggestive of similar therapeutic action hence; it is cheaper to use the lower dose. While a prolonged high ciprofloxacin concentration in skeletal muscle has therapeutic advantage for fish, it remains a public health concern because the muscle is an edible tissue.Keywords: Bath, Ciprofloxacin, ELISA, Pharmacokinetics, Tilapia

Pharmacokinetics of Ciprofloxacin in Broiler Chickens After Single Intravenous and Intraingluvial Administration

Abstract The trial was performed on 10 clinically healthy Ross hybrid chickens, 5 from each gender, weighing 2.75-2.84 kg. The tested quinolone was applied at the same dose for both routes of application - 10 mg/kg of body weight. Ciprofloxacin hydrochloridum 5% solution for i.v. and 1% solution for intraingluvial treatment were prepared. In a crossover study design, ciprofloxacin hydrochloridum was administered as 5 % solution for i.v. bolus injection to broiler chickens and after 14 days as 1 % solution for intraingluvial administration into a crop to the same birds. Serum ciprofloxacin concentrations were assayed by HPLC with UV detection at a wavelength of 279 nm. After intravenous injection the following pharmacokinetic parameters were determined: t1/2β = 9.07 h; t1/2α= 0.36 h; MRT = 10.20 h and MRT = 10.75 h; AUC0→∞ = 19.560 μg.h/mL and AUC0→∞ = 19.843 μg.h/mL. After intraingluvial application parameters determined by the two pharmacokinetic models were as: t1/2α= 0.86 h; t1/2β = 7,20 h and t1/2β = 7.89 h; MRT = 12.67 h and MRT = 12.93 h; AUC0→∞ = 11.340 μg.h/mL and AUC0→24 h = 11.973 μg.h/mL; Cmax = 2.841 μg/mL and Cmax = 2.638 μg/mL; Tmax = 0.48 h and Tmax = 0.39 h; t1/2abs. = 0.146 h; MAT = 2.47 h and MAT = 2.18 h; F = 57.91% and F = 63.89%. These results suggested that a dose of 10 mg/kg of body weight provides maximum plasma concentration ater intraingluvial administration and is effective in the control of many infectious diseases of poultry.

Population pharmacokinetic analysis of ciprofloxacin in the elderly patients with lower respiratory tract infections

The aims of the study were to develop a population pharmacokinetic model of ciprofloxacin (CPX) in the elderly patients and to examine the impact of patient-dependent variables on pharmacokinetic parameter values of this drug.The study was conducted in a group of 44 patients at the age of 44–96years, hospitalized due to pneumonia lobaris or bronchopneumonia. Patients received CPX at a dose of 200mg every 12h as a constant rate infusion over 0.5h. Concentrations of CPX in serum were measured by HPLC with UV detection.Population pharmacokinetic analysis revealed that CPX concentration versus time data were best described by a one-compartment model. The mean values of volume of distribution and clearance of CPX in the patients above 65years of age were 78.41±13.17L and 18.39±4.15L/h, respectively. The creatinine clearance influenced CPX clearance according to the equation: CLCPX (L/h)=8.0+0.21·CLCr, while the volume of distribution of CPX was dependent on the body weight of the patient as follows: VdCPX (L)=22.72+0.86·WT.In summary, the developed population model can be used to assess the pharmacokinetic parameters of CPX in the elderly patients and to select on the basis of these parameters and MIC values an optimal dosage regimen of this drug.

The ciprofloxacin target AUC : MIC ratio is not reached in hospitalized patients with the recommended dosing regimens

The aim of this study was to determine the ciprofloxacin serum concentrations in hospitalized patients and to determine which percentage reached the efficacy target of AUC : MIC > 125. Additionally, the influence of demographic anthropomorphic and clinical parameters on the pharmacokinetics and pharmacodynamics of ciprofloxacin were investigated. In serum of 80 hospitalized patients ciprofloxacin concentrations were measured with reverse phase high performance liquid chromatography with fluorescence detection. The ciprofloxacin dose was 400-1200 mg day(-1) i.v. in two or three doses depending on renal function and causative bacteria. Pharmacokinetic parameters were calculated with maximum a posteriori Bayesian estimation (MW\PHARM 3.60). A two compartment open model was used. Mean (± SD) age was 66 (± 17) years, the mean clearance corrected for bodyweight was 0.24 l h(-1) kg(-1) and the mean AUC was 49 mg l(-1) h. Ciprofloxacin clearance and thus AUC were associated with both age and serum creatinine. Of all patients, 21% and 75% of the patients, did not reach the proposed ciprofloxacin AUC : MIC > 125 target with MICs of 0.25 and 0.5 mg l(-1), respectively. A computer simulated increase in the daily dose from 800 mg to 1200 mg, decreased these percentages to 1% and 37%, respectively. A substantial proportion of the hospitalized patients did not reach the target ciprofloxacin AUC : MIC and are suboptimally dosed with recommended doses. Taking into account the increasing resistance to ciprofloxacin worldwide, a ciprofloxacin dose of 1200 mg i.v. daily in patients with normal renal function is necessary to reach the targeted AUC : MIC > 125.

In vivo ciprofloxacin release from hydroxyapatite-based bone implants in rabbit tibia: a preliminary study.

The present study deals with the preliminary evaluation of in vivo ciprofloxacin release from HAp-ciprofloxacin bone implants in rabbit tibia. The HAp-ciprofloxacin implants (2 × 2.5 mm) were prepared using various HAp-ciprofloxacin composites synthesized by precipitation technique and 1.5% w/v guar gum as a binder. 5 implants were implanted in artificial cortical bone window at the right proximal tibia of each rabbit. After 3- and 6-day intervals, the rabbits were euthanized. Bone marrow and serum concentrations of ciprofloxacin were determined from the harvested tibia using HPLC method. The results displayed the availability of elevated local antibiotic concentration at the implanted site with the limitation of systemic antibiotic exposure, which can be useful to minimize the risk of systemic toxicity-related side effects. This study is the preliminary investigation of the suitability of in vivo ciprofloxacin release from HAp-ciprofloxacin bone implants in rabbit tibia, after implantation, and these implants can be useful for the treatment of bacterial bone infections like osteomyelitis.

Optimizing ciprofloxacin dosing in intensive care unit patients through the use of population pharmacokinetic-pharmacodynamic analysis and Monte Carlo simulations

To explore different ciprofloxacin dosage regimens for the treatment of intensive care unit (ICU) patients with respect to clinical outcome and the development of bacterial resistance for the major Gram-negative pathogens. A population pharmacokinetic model was first developed on ciprofloxacin serum concentrations obtained in 102 ICU patients. Then, based on this model, pharmacokinetic-pharmacodynamic Monte Carlo simulations (MCSs) were carried out to explore the appropriateness of different ciprofloxacin dosage regimens in ICU patients. The defined targets were free AUC(24)/MIC ≥90 h (as a predictor of clinical outcome) and T(MSW) ≤20% (as a predictor of selecting resistance), where T(MSW) is the time spent within the mutant selection window over 24 h. Two simulation trials were conducted: Trial 1 took into account the whole MIC distribution for each causative pathogen in line with empirical antibiotherapy; Trial 2 used MIC breakpoints given by the Antibiogram Committee of the French Microbiology Society in order to treat the 'worst-case' scenario. Trial 1 showed that for Pseudomonas aeruginosa and Acinetobacter baumannii, the common dosage regimens of 400 mg twice or three times a day did not achieve the desired target attainment rates (TARs) with respect to T(MSW), while suboptimal TARs were found for AUC(24)/MIC. Trial 2 showed that ≤ 18% of patients reached the target of T(MSW) ≤ 20% for MIC breakpoints of 0.5 and 1 mg/L, regardless of the administered dose. Based on the mutant selection window concept, our simulations truly question the use of ciprofloxacin for the treatment of P. aeruginosa and A. baumannii infections in ICU patients due to the potential for developing resistance.

씨프로바이정 (시프로플록사신 250 mg)에 대한 로프신정의 생물학적 동등성평가

The purpose of the present study was to evaluate the bioequivalence of two ciprofloxacin tablets, Ciprobay (Bayer Korea Ltd.) and Rofcin (Binex Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). The release of ciprofloxacin from the two ciprofloxacin tablets in vitro was tested using KP XIII Apparatus I method with dissolution media (0.01 M HCl). The dissolution profiles of two ciprofloxacin tablets were very similar at dissolution media. Twenty four healthy male volunteers were divided into two groups and a randomized 22 cross-over study was employed. After one tablet (250 mg ciprofloxacin) was orally administrated, blood was taken and the concentrations of ciprofloxacin in serum were determined using HPLC with UV detector. The pharmacokinetic parameters such as were calculated. The results showed that the differences in between two ciprofloxacin tablets based on the Ciprobay were -0.63%, 3.98% and -9.23%, respectively. There were no sequence effects between two tablets in these parameter. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log(0.8) to log(1.25)(e.g., log(0.9520)~log(1.0523) and log(0.9689)~log(1.1663) for , respectively). Thus, Rofcin tablet was bioequivalent to Ciprobay tablet.

Effect of Chloroquine on the Bioavailability of Ciprofloxacin in Humans

Chloroquine, a front-line drug in the treatment of malaria, has developed widespread resistance, especially to the Plasmodium falciparum strains. Ciprofloxacin is a second-generation quinolone used as a broad-spectrum fluoroquinolone antibacterial agent. The possibility of using ciprofloxacin as an antimalarial, especially in chloroquine-resistant strains, is very promising. They concluded from in vitro studies however that the anti-malarial effect occur at high dose level of ciprofloxacin to achieve the required serum concentrations. Studies have shown that there is little interstrain variability in the in vitro susceptibility of P. falciparum to fluoroquinolones. There is also no cross-resistance between them. Another study stated that 50% inhibition of parasite growth in vitro required 6.6 microg/mL after a high dose of ciprofloxacin was used. They thus concluded that ciprofloxacin should not be used alone. There is need for in vivo studies to ascertain the achievable serum concentration of ciprofloxacin when given alone and when given in combination with chloroquine. The serum concentration of ciprofloxacin was studied when ciprofloxacin was given alone and in combination with chloroquine in humans. Five healthy male volunteers aged (19-31) years who were not taking any of the prescribed medications and had no sensitivity to either ciprofloxacin or chloroquine, each received 500 mg ciprofloxacin orally with 250 mL of water, and after a 2-week wash-out period, 500 mg ciprofloxacin plus 600 mg of chloroquine was administered orally with 250 mL of water after informed consent. A blood sample (2.5 mL) was collected just before taking the drug at 8:00 AM representing 0 hours and continued afterward at 1, 2, 4, 8, 12, and 24 hours the following day. Serum samples were stored at -20 degrees C until analyzed. The minimal inhibitory concentrations (MIC) by diffusion through agar technique was used for the assay of serum ciprofloxacin. The following bioavailability parameters: Cmax, tmax, and AUC 0-24, AUC 0-infinity were calculated. The peak serum concentration Cmax of ciprofloxacin was 3.42 +/- 0.32 microg/mL, which dropped to 2.8 +/- 0.18 microg/mL when chloroquine was taken together with ciprofloxacin. These values were less than the in vitro 12.5 microg/mL concentrations required to inhibit P. falciparum. Though the effect of parasitemia was not ascertained, the in vivo use of ciprofloxacin alone or in combination is doubtful because increasing the dose that will reach the in vitro level will lead to toxicity in vivo.

Pharmacokinetics of Enrofloxacin and Its Metabolite Ciprofloxacin in Male and Female Turkeys following Intravenous and Oral Administration

The pharmacokinetics of enrofloxacin (EFL) was investigated in turkeys (6 male and 6 female; 7-month-old at the start of the experiment), after intravenous and oral administration at a dose of 10 mg/kg body weight. The serum concentrations of EFL and its active metabolite ciprofloxacin (CFL) were determined by high-performance liquid chromatography. The serum concentrations vs time were analysed by a compartmental analysis. The mean values of EFL pharmacokinetic parameters showed differences only between values of V(d,ss) (3.46+/-0.19 for the females and 4.53+/-0.11 L/kg for the males, p>0.05). The metabolite CFL was eliminated more slowly than its parent compound. There were no statistically significant differences between the values of the CFL pharmacokinetic parameters calculated for both sexes, excluding the higher values (p>0.05) of C(max) in the females. The ratio AUC(CFL)/AUC(EFL)x100 was 4.4% in the male and 6.84% in the female birds. After oral administration of EFL the values of F(%) were 77.83 in the female and 79.61 in the male turkeys. Higher CFL serum concentrations were measured in females (p>0.05). The pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in turkeys can be characterized as similar to that in chickens and very similar between both sexes.

Reliable New High-Performance Liquid Chromatographic Method for the Determination of Ciprofloxacin in Human Serum

Ciprofloxacin is a broad-spectrum antibacterial drug, being used in a wide range of infections. A method to quantify the total (unbound + protein-bound) ciprofloxacin concentrations in human serum is presented based on rapid liquid-liquid extraction, followed by reversed-phase liquid chromatography and UV detection at 280 nm. The calibration range used was 2 to 10 mg/L. The mean accuracy and precision (CV%) were all within specifications: at 0.2 mg/L 81.2% (10.1%), assigned to be the lower limit of quantification (LLOQ), at 8 mg/L 103.6% (4.48%), at 14 mg/L 103.1% (3.98%). Metabolites and frequently used comedications showed minimal interference. Sample storage conditions suitable for routine determination of serum ciprofloxacin concentrations for daily therapeutic drug monitoring (gel-collection tubes and PVC tubes at 4 degrees C) and for intermittent batch-wise analyses for research purposes (PVC tubes at -18 degrees C) showed acceptable sample stability after storage for 48 hours (4 degrees C) and 6 months (-18 degrees C).

Pharmacokinetic/Pharmacodynamic (PK/PD) Evaluation of a Once-Daily Treatment Using Ciprofloxacin in an Extended-Release Dosage Form*

To evaluate the suitability of a once-a-day dosing regimen of ciprofloxacin using a new extended-release dosage form based on PK/PD principles. Ciprofloxacin's serum concentrations were measured after administration of 500 mg immediate-release twice-daily, and 1,000 mg extended-release once-daily to 19 healthy volunteers. Pharmacokinetic parameters were determined using non-compartmental and compartmental data analysis. Measured serum concentration profiles were linked to ciprofloxacin's effect against Escherichia coli (MIC 0.013 mg/l) from in vitro kill curve studies where the pharmacokinetics of ciprofloxacin were simulated and change in number of bacteria (CFU/ml) versus time was monitored. Resulting parameters were used to compare expected kill curves for the two dosing regimens based on measured ciprofloxacin concentrations. Fitting the data using an appropriate PK/PD model resulted in a set of mean pharmacodynamic parameters (bacterial growth rate constant, k0, maximum kill rate constant, Kmax, and EC50). The model included a novel term to account for a change in kill rate after approximately 4 h when Kmax decreased in concentration-dependent matter. The model allowed excellent curve fits of all ciprofloxacin concentrations investigated. Comparison of expected kill curves with the immediate-release versus extended-release treatments showed similar outcome. Both treatments resulted in a decrease in CFU/ml > 5 log units over 24 h. Results indicate that once-a-day dosing of equal total daily doses with the new and more compliance-friendly extended-release dosing form will be therapeutically equivalent to once-a-day dosing with traditional immediate-release dosage forms for treatment of infections with this microorganism.

The gingival crevicular fluid ciprofloxacin level in subjects with gingivitis and periodontitis, and its effects on clinical parameters

The purpose of this study, conducted on patients with gingivitis and periodontitis, was twofold: to find out the serum and gingival crevicular fluid concentration of ciprofloxacin, which is a common drug used effectively against Actinobacillus actinomycetemcomitans and to determine the effects of ciprofloxacin administration on clinical parameters. A total of 32 adult patients, consisting of 16 subjects with gingivitis and 16 subjects with untreated chronic periodontitis, were included in the study. The subjects were divided into four groups: group I included eight subjects with chronic gingivitis who had not previously received any ciprofloxacin; group II included eight subjects with chronic gingivitis to whom three doses of ciprofloxacin were administered (Siprosan 500 mg) to establish adequate gingival crevicular fluid and serum concentrations of the agent; group III consisted of eight subjects with chronic periodontitis who had not received any ciprofloxacin; group IV included eight subjects with chronic periodontitis to whom three doses of ciprofloxacin were administered to establish adequate gingival crevicular fluid and serum concentrations of the agent. All patients were systemically healthy, free of pain and reported no current medication usage. Each patient was treated with scaling and/or root planing using specific hand instruments under local anesthesia. Gingival index, plaque index and clinical attachment levels of the teeth were used to determine the clinical condition of the subjects and findings were recorded at the beginning, seventh day, 21st day and third month of the study. Serum ciprofloxacin level was measured in venous blood. Approximately 5 ml of venous blood was drawn from subjects in groups II and IV using a standard venipuncture technique. Gingival crevicular fluid samples were sampled from six interproximal sites with six paper strips in the posterior region of upper jaw (excluding third molar) and all gingival crevicular fluid and serum samples were evaluated by high-performance liquid chromatography. The serum concentrations of ciprofloxacin at the first and 72nd hour were not significantly different in subjects with periodontitis compared to subjects with gingivitis. But the gingival crevicular fluid concentrations of ciprofloxacin at the same hours were significantly high in subjects with periodontitis compared to subjects with gingivitis. Both subjects with gingivitis and periodontitis had significantly higher ciprofloxacin levels in the gingival crevicular fluid than in serum. The application of ciprofloxacin did not have any positive or statistically significant effect upon the clinical parameters of the subjects with gingivitis. On the other hand, a significant decrease in the clinical attachment level scores of the subjects with periodontitis (group IV) was observed compared to group III in the 21st day and third month. According to these results, the use of ciprofloxacin as an alternative drug in subjects with periodontitis but not gingivitis can be recommended. However, long-term studies are also needed to assess the effects of ciprofloxacin on clinical parameters.

Efficacy of bioabsorbable antibiotic containing bone screw in the prevention of biomaterial-related infection due to Staphylococcus aureus

Impregnation of antimicrobial agents within biodegradable orthopedic implants provides a possibility for local antimicrobial prophylaxis of biomaterial-related infections. The objective of this study was to evaluate the efficacy of a bioabsorbable ciprofloxacin containing bone screw (Ab-PLGA) in the prevention of biomaterial-related infection due to Staphylococcus aureus in a rabbit model. Animals in Group I ( n = 8) received a Ab-PLGA screw contaminated with S. aureus, while animals in Group II ( n = 8) received a stainless steel (SS) screw contaminated with S. aureus. In two negative control groups, the animals received a Ab-PLGA screw (Group III, n = 4) or a SS screw (Group IV, n = 4) without bacterial contamination. 18F-FDG-PET imaging, performed at 6 weeks, was applied as a novel quantitative in vivo imaging modality of implant-related infection. Infection was verified by swab cultures, direct cultures of the retrieved implant, and quantitative cultures of pulverized bone. The concentrations of ciprofloxacin in serum and local bone tissue were determined by a high performance liquid chromatographic (HPLC) method with fluorescence (FLD) detection. In the group of contaminated Ab-PLGA screws, all cultures were negative. In the group of contaminated SS screws, all cultures of retrieved implants and six cultures out of eight of pulverized bone were positive for inoculated S. aureus. In negative control groups, all cultures were negative except one contaminant ( S. cohnii) found in a SS screw culture. Verified infection of contaminated SS screws was collaborated by the increased 18F-FDG-PET uptake ( P = 0.004 compared with the group of contaminated Ab-PLGA screws). The mean bone tissue concentration of ciprofloxacin varied from 2.54 to 0.83 μg/g bone as a function of distance from the implantation site. The serum concentration of ciprofloxacin remained undetectable and below the resolution of the analytic method (<5.0 ng/ml). This study confirmed the in vivo efficacy of bioabsorbable antibiotic containing bone screw in the prevention of biomaterial-related infection due to S. aureus.

A Population Pharmacokinetic–Metabolism Model for Individualizing Ciprofloxacin Therapy in Ophthalmology

The purpose of this study was to construct a population pharmacokinetic (PK) metabolism (MB) model to describe ciprofloxacin (C) concentrations in plasma and vitreous and aqueous humors in 26 patients. Ciprofloxacin was given as a 3-day oral prophylactic treatment to 26 patients before vitrectomy. Plasma, vitreous, and aqueous humor samples were collected from patients at different times on the day of surgery. Patients were phenotyped for CYP 1A2 activity using caffeine. Ciprofloxacin and caffeine concentrations were determined using validated HPLC assays. All concentrations of ciprofloxacin were simultaneously modeled using a four-compartment PK-MB model. Creatinine clearance and CYP 1A2 activity were modeled as surrogate markers of renal and hepatic clearances, respectively. Population PK was performed with IT2S, and simulations were performed with ADAPT-II. No eye infections were observed in any of the patients enrolled in the study, and there were only minimal effects on vitreous and aqueous concentrations after ocular drops were added to the oral treatments. The model that best described the concentrations of ciprofloxacin in serum and in aqueous and vitreous humor was a four-compartment PK linear model. Simulated AUCs of ciprofloxacin mean concentrations in the aqueous and vitreous humors were 17 +/- 9 and 10 +/- 8% of the systemic AUC, respectively. The terminal elimination half-life of the compound was (mean +/- SD) 5.0 +/- 2.8 hours. The apparent volume of distribution (Vss/F) was calculated to be 122.1 +/- 39.7 L. This PK-MB model may be very useful in optimizing treatments of various eye infections with ciprofloxacin. The results of this study suggest that giving ciprofloxacin orally for 2 days preceding surgery may prevent endophthalmitis from occurring, consequently abrogating the need for administering antibiotics via intraocular injections.

In vivo interaction between ciprofloxacin hydrochloride and the pulp of unripe plantain (Musa paradisiaca).

The absorption of quinolone antibiotics is seriously impaired by polyvalent cations due to the formation of unabsorbable complexes. M. paradisiaca Linn. (Musaceae), an important staple food in most parts of the world, has been demonstrated to contain many polyvalent cations. The aim of the work was to study the influence of concurrent administration of M. paradisiaca and ciprofloxacin HCI on the pharmacokinetic profiles of ciprofloxacin. The study was carried out in two phases in five healthy male rabbits. Phase one involved oral administration of ciprofloxacin (40 mg/kg) to rabbits, withdrawing blood from the marginal ear vein at 1, 2, 4, and 24 h intervals and checking the serum ciprofloxacin concentration. After a one-week drug "wash-out" period, the second phase started with concurrent oral administration of M. paradisiaca (800 mg/kg) and ciprofloxacin (40 mg/kg). Blood was again withdrawn and analyzed for serum ciprofloxacin content. Antimicrobial activity of the serum was also assessed and expressed as reciprocal serum inhibitory titer. Co-administration of both agents resulted in significant (P<0.05) decrease in serum concentration of ciprofloxacin at all the time interval except at the 24th hour. The following pharmacokinetic parameters were also decreased: area under the curve (81.53%), peak serum concentration (94.37%), elimination rate constant (42.35%); while increase in half-life (81.08%) and clearance rate (69.64%) were noted. Antimicrobial study showed that the antimicrobial potency against E. coli was also decreased by such concurrent administration. The pharmacokinetic parameters and antimicrobial activities of ciprofloxacin were significantly decreased when it was given concurrently with pulp of unripe plantain. Complex formation between the drug and the polyvalent cations present in plantain, leading to decrease in absorption and hence bioavailability, may be responsible for the observed antagonistic interactions.

The effect of pharmacokinetics on the bactericidal activity of ciprofloxacin and sparfloxacin against Streptococcus pneumoniae and the emergence of resistance.

The pharmacokinetics of ciprofloxacin and sparfloxacin were simulated in vitro and the effects of pharmacodynamic parameters on bactericidal activity and the emergence of quinolone resistance were examined for Streptococcus pneumoniae. Simulated serum concentrations of ciprofloxacin 500 mg bd were more rapidly bactericidal than sparfloxacin 200 mg bd, despite lower values for the key pharmacodynamic parameters (AUC/MIC and C(max)/MIC). This was possibly related to the slower oral absorption of sparfloxacin, which delayed achievement of the MIC compared with ciprofloxacin. In addition, sparfloxacin was shown to have similar bactericidal activity to ciprofloxacin when tested at the same concentrations, despite its four-fold better potency in MIC terms. The emergence of resistance following exposure to ciprofloxacin appeared to be dependent on the C(max)/MIC ratio and the AUC above the MIC, but not the AUC/MIC ratio. Resistance (at least four-fold increase in MIC) developed when the C(max)/MIC ratio was less than four or the AUC above the MIC was less than 10, and the resulting cultures regrew fully. In contrast, pneumococci with a two- to four-fold increase in sparfloxacin MIC were selected in the presence of serum concentrations of sparfloxacin despite a C(max)/MIC ratio higher than 12, but these isolates remained clinically susceptible by breakpoint MIC and their growth was inhibited by repeated dosage of sparfloxacin. Nevertheless, the selection of pneumococci with reduced susceptibility, and the possibility of further mutation to highly resistant strains supports the use of quinolones that rapidly eradicate pneumococci at conventional doses and achieve concentrations, in both serum and tissues, which exceed at least 4 x MIC.