Pharmacokinetic profiles of levofloxacin after intravenous, intramuscular and subcutaneous administration to rabbits (Oryctolagus cuniculus) (original) (raw)
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Antimicrobial agents and chemotherapy, 1998
The safety and pharmacokinetics of once-daily oral levofloxacin in 16 healthy male volunteers were investigated in a randomized, double-blind, placebo-controlled study. Subjects were randomly assigned to the treatment (n = 10) or placebo group (n = 6). In study period 1, 750 mg of levofloxacin or a placebo was administered orally as a single dose on day 1, followed by a washout period on days 2 and 3; dosing resumed for days 4 to 10. Following a 3-day washout period, 1 g of levofloxacin or a placebo was administered in a similar fashion in period 2. Plasma and urine levofloxacin concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters were estimated by model-independent methods. Levofloxacin was rapidly absorbed after single and multiple once-daily 750-mg and 1-g doses with an apparently large volume of distribution. Peak plasma levofloxacin concentration (Cmax) values were generally attained within 2 h postdose. The mean values of Cmax and are...
Research in Veterinary Science, 2020
The aim of this study was to assess the pharmacokinetic profile of LFX in sheep after intravenous (IV) and oral (PO) administration of 2 mg/kg LFX once a day for 5 days and to evaluate its tissue depletion in the muscles, heart, liver, lungs, and kidneys. Twenty healthy female sheep were randomly divided into two equal groups. Each group was further randomly subdivided into two equal subgroups (n = 5). Group 1 was used for blood collection and underwent a crossover design (2 × 2 Latin square). Group 2 was randomly subdivided into two equal subgroups (n = 5) for IV and PO route respectively, and used for tissue collection. A single sheep was sacrificed at each time point and the organs were harvested. Samples were analyzed using a validated HPLC method with fluorescence detection. LFX administered orally was rapidly absorbed with a peak plasma concentration of 2866 ± 239 ng/mL and an absolute oral bioavailability of 114 ± 27.7%. The pharmacokinetic estimates were comparable between PO and IV administration. According to the pharmacokinetic/pharmacodynamic surrogate index (area under the curve / minimum inhibitory concentration) of 100-125, LFX has the potential to be an effective treatment for infections caused by bacteria with a MIC of 0.049-0.061 μg/mL. LFX was detected for up to 48 h in all the tissues samples. The kidney had the highest LFX concentration after IV and PO administration. The AUC tissue/plasma ratio was lower than 1 in all tissues indicating absence of LFX tissue accumulation.
Pharmacodynamics of Levofloxacin
JAMA, 1998
Context.-One purpose of early clinical trials is to establish the appropriate dose of an antibiotic for phase 3 trials. Development of a relationship between the ratio of drug exposure to organism minimum inhibitory concentration (MIC) and therapeutic response early in the development process would allow an optimal choice of dose to maximize response. Objective.-To prospectively quantitate the relationship between plasma levels of levofloxacin and successful clinical and/or microbiological outcomes and occurrence of adverse events in infected patients. Design.-Multicenter open-label trial. Setting.-Twenty-two enrolling university-affiliated medical centers. Patients.-A total of 313 patients with clinical signs and symptoms of bacterial infections of the respiratory tract, skin, or urinary tract. Main Outcome Measures.-Clinical response and microbiological eradication of pathogenic organisms. Results.-Of 313 patients, 272 had plasma concentration-time data obtained. Of these, 134 patients had a pathogen recovered from the primary infection site and had an MIC of the pathogen to levofloxacin determined. These patients constituted the primary analysis group for clinical outcome. Groups of 116 and 272 patients, respectively, were analyzed for microbiological outcome and incidence of adverse events. In a logistic regression analysis, the clinical outcome was predicted by the ratio of peak plasma concentration to MIC (Peak/MIC) and site of infection (PϽ.001). Microbiological eradication was predicted by the Peak/MIC ratio (PϽ.001). Both clinical and microbiological outcomes were most likely to be favorable if the Peak/ MIC ratio was at least 12.2. Conclusions.-Levofloxacin generated clinical and microbiological response rates of 95% and 96%, respectively. These response rates included fluoroquinolone "problem pathogens," such as Streptococcus pneumoniae and Staphylococcus aureus. Exposure to levofloxacin was significantly associated with successful clinical and microbiological outcomes. The principles used in these analyses can be applied to other classes of drugs to develop similar relationships between exposure and outcome. This pharmacokinetic modeling could be used to determine optimal treatment dose in clinical trials in a shorter time frame with fewer patients. This modeling also should be evaluated for its potential to improve outcomes (maximizing therapeutic response, preventing emergence of resistance, and minimizing adverse events) of patients treated with this drug.
Pharmacokinetic studies of levofloxacin after oral administration in healthy and febrile cow calves
Veterinary Research Communications, 2009
The present experiment was designed to study the pharmacokinetics of levofloxacin in six healthy cross bred female cow calves (4 to 6 months age) weighing between 40 to 80 kg. Plasma from blood was separated by centrifugation at 10,000 rpm. Quantitative estimation of levofloxacin was done by UV-VIS spectrophotometer at 286 nm. The mean maximum plasma concentration (Cpmax ) of levofloxacin in febrile calves (5.28 ± 0.32 µg/ml) did not differ significantly as compared with healthy calves (4.50 ± 0.22 µg/ml) after single dose (20 mg/kg) oral administration. The mean therapeutic plasma concentration ( Cpther ) of levofloxacin was maintained for longer period in febrile calves (10 h) as compared to healthy calves ( 8 h). The mean maximum urine concentration (Cumax) in febrile (40.86 ± 2.19 µg/ml) also did not differ significantly as compared with healthy calves (39.38 ± 2.43 µg/ml). No significant difference in various pharmacokinetic parameters of plasma was observed in healthy calves ( β = 0.23 ± 0.01/h ; t1/2 β = 3.00 ± 0.17 h and MRT = 4.66 ± 0.14 h ) and febrile calves ( β = 0.23 ± 0.01/ h; t1/2 β = 3.05 ± 0.16 h and MRT = 5.04 ± 0.14 h ) . The mean value of β, and t ½ β calculated in urine also did not differ between healthy and febrile calves. However, the value of MRT(3.79 ± 0.07 h) and ClB(1.65 ± 0.09 ml/kg/min) calculated in urine of febrile calves significantly(p < 0.05) differ to healthy calves(MRT = 3.15 ± 0.03 h;ClB = 2.09 ± 0.13 ml/kg/min). Based on kinetic profile levofloxacin may be given orally at the dose rate of 1.49 mg/kg B.W.at 8 h intervals in febrile calves.
Pharmacokinetics of intravenously administered levofloxacin in men and women
Pharmacotherapy
To characterize and compare the pharmacokinetics of levofloxacin in men and women after systemic administration. Prospective, open-label, parallel group pharmacokinetic study. University research center. Eleven healthy men and nine healthy women stratified by body mass index. Subjects received levofloxacin as a single 500-mg intravenous dose. Serum and urine were collected over 36 hours. Levofloxacin concentrations were determined by high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic analysis was performed with ADAPT II software (University of Southern California, Los Angeles, CA). Median (range) body mass index was 23.2 kg/m2 (19.9-28.3 kg/m2) for men and 23.6 kg/m2 (16.0-32.4 kg/m2) for women (p = 0.67). A two-compartment model best fit the pharmacokinetic data: median (range) R2 was 0.996 (0.990-0.999). Women had a 24% greater exposure to levofloxacin, with a significantly smaller steady-state volume of distribution (p < 0.01) and a slower clear...
Pharmacokinetic Study of Two Oral Formulations of Levofloxacin in Healthy Male Volunteers
2006
The objective of this study was to compare different pharmacokinetic parameters of a local ("X") and reference (Tavanic) formulations of levofloxacin 250 mg tablets after oral administration of a single dose under fasting condition. Thirteen blood samples were collected from each of the eight Bangladeshi healthy male volunteers over 24 hours after oral administration of the drugs. Serum levofloxacin concentrations were determined by HPLC assay using UV detection, and pharmacokinetic parameters were determined by the non-compartmental method. Mean ± SD of C max , AUC 0-24 , AUC 0-α , T max , t 1/2 , k el , were 4.33 ± 1.16 and 4.56 ± 1.51 µg/mL, 45.90 ± 8.74 and 37.77 ± 9.94 hr-µg /mL, 79.94 ± 32.80 and 66.85 ± 35.43 hr-µg/mL, 1.22 ± 0.49 and 1.28 ± 0.41, 19.90 ± 11.49 and 21.00 ± 16.39 hr, 0.04 ± 0.02 and 0.05 ± 0.03 hr -1 for the local ("X") and reference formulation, respectively. From the paired t-test, the p-values for two formulations were found to be 0.182, 0.412 and 0.725 for AUC 0-24 , AUC 0-α , and C max respectively. The 90% confidence intervals of the mean of the difference between log-transformed values for C max were almost within the bioequivalence accepted range of 80% to 125%, namely: (78.90%, 118.36%); but for AUC 0-24 and AUC 0-α the values were are beyond the acceptable range. (100.83%, 146.52%) and (94.34%, 157.89%) respectively. The results indicate that the two formulations are not bioequivalent for both the rate and extent of absorption.
Pharmacokinetic Study of Two Oral Formulations of Levofloxacin in Healthy Male Volunteersl
Dhaka University Journal of Pharmaceutical Sciences, 2007
The objective of this study was to compare different pharmacokinetic parameters of a local ("X") and reference (Tavanic) formulations of levofloxacin 250 mg tablets after oral administration of a single dose under fasting condition. Thirteen blood samples were collected from each of the eight Bangladeshi healthy male volunteers over 24 hours after oral administration of the drugs. Serum levofloxacin concentrations were determined by HPLC assay using UV detection, and pharmacokinetic parameters were determined by the non-compartmental method. Mean ± SD of C max , AUC 0-24 , AUC 0-α , T max , t 1/2 , k el , were 4.33 ± 1.16 and 4.56 ± 1.51 µg/mL, 45.90 ± 8.74 and 37.77 ± 9.94 hr-µg /mL, 79.94 ± 32.80 and 66.85 ± 35.43 hr-µg/mL, 1.22 ± 0.49 and 1.28 ± 0.41, 19.90 ± 11.49 and 21.00 ± 16.39 hr, 0.04 ± 0.02 and 0.05 ± 0.03 hr -1 for the local ("X") and reference formulation, respectively. From the paired t-test, the p-values for two formulations were found to be 0.182, 0.412 and 0.725 for AUC 0-24 , AUC 0-α , and C max respectively. The 90% confidence intervals of the mean of the difference between log-transformed values for C max were almost within the bioequivalence accepted range of 80% to 125%, namely: (78.90%, 118.36%); but for AUC 0-24 and AUC 0-α the values were are beyond the acceptable range. (100.83%, 146.52%) and (94.34%, 157.89%) respectively. The results indicate that the two formulations are not bioequivalent for both the rate and extent of absorption.