-
Blood Purification 2018To analyse the effect of haemodiafiltration (CVVHDF) flow rate on amikacin pharmacokinetics and blood concentrations. (Clinical Trial)
Clinical Trial Observational Study
BACKGROUND
To analyse the effect of haemodiafiltration (CVVHDF) flow rate on amikacin pharmacokinetics and blood concentrations.
METHODS
Prospective observational study. Patients receiving CVVHDF and amikacin treatment were included. Pharmacokinetic parameters were calculated using Bayesian analysis. Spearman correlation test was used in order to assess the influence of CVVHDF flux on amikacin minimum concentration (Cmin) and plasma clearance.
RESULTS
Thirty patients undergoing CVVHDF procedures were included. The treatment with amikacin started at an initial mean dose of 12.4 (4.1) mg/kg/day. An association between the flow rate and Cmin value (r = 0.261; p = 0.161) and plasma clearance was found (r = 0.268; p = 0.152). Four patients (13.3%) were not able to achieve peak concentration over MIC value higher than 8. In 4 patients, amikacin had to be discontinued due to a high Cmin value.
CONCLUSIONS
Amikacin clearance in patients with CVVHDF is affected by the flow rate used. Therefore, CVVHDF dose should be taken into account when dosing amikacin.
Topics: Aged; Amikacin; Critical Illness; Female; Hemodiafiltration; Humans; Male; Middle Aged
PubMed: 29232669
DOI: 10.1159/000478969 -
JAMA Feb 1977Amikacin sulfate was administered to 18 patients for the treatment of 19 severe infections. Seventeen infections were caused by gentamicin-resistant Gram-negative...
Amikacin sulfate was administered to 18 patients for the treatment of 19 severe infections. Seventeen infections were caused by gentamicin-resistant Gram-negative bacilli, and 13 patients were bacteremic. Bacteriologic cure was attained in all but one instance, and effective serum, bile, and pleural fluid drug levels were demonstrated. Drug-related fever occurred in one patient, and another experienced a maculopapular rash and monilial intertrigo. In three patients, reversible renal toxicity developed, but none had clinical evidence of ototoxicity. Amikacin sulfate in a dose of 15 mg/kg/day is an effective antibiotic for the treatment of serious Gram-negative infections, particularly those due to gentamicin-resistant organisms.
Topics: Adult; Aged; Amikacin; Bacterial Infections; Enterobacteriaceae; Enterobacteriaceae Infections; Gentamicins; Humans; Kanamycin; Kidney; Klebsiella Infections; Middle Aged; Pseudomonas Infections; Sepsis
PubMed: 576282
DOI: No ID Found -
International Journal of Pharmaceutics Jul 2007Strong covalent immobilization of amikacin on Uni-Graft((R)) DV straight vascular prostheses made of gelatine-sealed poly(ethylene terephthalate) fibres was performed...
Strong covalent immobilization of amikacin on Uni-Graft((R)) DV straight vascular prostheses made of gelatine-sealed poly(ethylene terephthalate) fibres was performed according to procedure described in the Polish Patent No. P-358934. The concentrations of amikacin in sample solutions were estimated either by HPLC or by UV spectroscopy method previously optimized for amikacin measurements. A high correlation was found between these two methods. It was found that the antibiotic was bound in mixed-type way via three types of interactions: strong covalent bonds (dominating amount: 81.84%) and weak interactions: physical adsorption and ionic bonds (18.19%). Even when total amount of physically and ionically attached drug has been released, the remaining covalently bound amount still locally protected the prostheses in vitro against bacteria. The release test was conducted in PBS at pH 7.4 at 37 degrees C and showed that about 15% of total drug amount was eluted from the matrix during the first 7 days of shaking, then no more antibiotic was released. It suggested that about 85% of amikacin attached to prosthesis modified in mixed-type mode was bound via covalent interactions. A bacterial inhibition test on Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 27853 showed inhibition of growth for all strains at low inoculum concentrations up to 30 days as well as high inoculum concentration for E. coli. At high concentrations of S. aureus and P. aeruginosa, the modified prostheses showed slight bacteriostatic effect since 10th day of experiment. Amikacin-modified vascular prostheses might therefore be protected against bacterial infection locally, without long-lasting drug release to human system.
Topics: Amikacin; Anti-Bacterial Agents; Bacterial Infections; Blood Vessel Prosthesis; Chromatography, High Pressure Liquid; Drug Carriers; Humans; Microbial Sensitivity Tests; Postoperative Complications
PubMed: 17376617
DOI: 10.1016/j.ijpharm.2007.02.016 -
Luminescence : the Journal of... Jun 2022An aminoglycoside antibiotic, amikacin, is used to treat severe and recurring bacterial infections. Due to the absence of a chromophore, however, amikacin must be...
An aminoglycoside antibiotic, amikacin, is used to treat severe and recurring bacterial infections. Due to the absence of a chromophore, however, amikacin must be extensively derivatized before being quantified, both in analytical and bioanalytical samples. In this study, for the first time, we developed a simple and sensitive method for measuring amikacin sulfate using spectrofluorimetry with a 96-well plate reader, based on the design of the experiment's approach. To develop a robust and reproducible spectrofluorimetric method, the influence of essential attributes, namely pH of the buffer, heating temperature, and concentration of reagents, were evaluated using univariate analysis followed by multivariate analysis (central composite design). International Conference of Harmonization guidelines were used to validate the optimized method. The developed technique is linear from 1.9 to 10 μg/ml with a regression coefficient of 0.9991. The detection and quantification limits were 0.649 μg/ml and 1.9 μg/ml, respectively. For the developed method, both intraday and interday precision (%RSD) were less than 5%. Using the method, amikacin concentrations were quantified in prepared amikacin liposomes and commercial formulations of Amicin®. The developed method greatly reduces sample volume and is a rapid, high throughput microplate-based fluorescence approach for the convenient and cost-effective measurement of amikacin in pharmaceutical formulations. In comparison with previously published approaches, the suggested method allowed for quick analysis of a high number of samples in a short amount of time (96 samples in 125 sec), resulting in an average duration of analysis of 1.3 sec per sample.
Topics: Amikacin; Anti-Bacterial Agents; Drug Compounding; Fluorometry
PubMed: 35322527
DOI: 10.1002/bio.4238 -
Antimicrobial Agents and Chemotherapy Jun 1978Adult volunteers underwent a single lumbar puncture 1 to 8.5 h after one 7.5-mg/kg intramuscular amikacin injection. Eighteen showed no detectable drug in cerebrospinal...
Adult volunteers underwent a single lumbar puncture 1 to 8.5 h after one 7.5-mg/kg intramuscular amikacin injection. Eighteen showed no detectable drug in cerebrospinal fluid; six had concentrations <0.5 mug/ml.
Topics: Adult; Amikacin; Humans; Kanamycin; Time Factors
PubMed: 677857
DOI: 10.1128/AAC.13.6.1042 -
Diagnostic Microbiology and Infectious... Jun 2021This study aims to compare the bacterial killing of once- versus twice-daily nebulized amikacin against Pseudomonas aeruginosa and to determine the optimal duration of...
Pharmacodynamics of once- versus twice-daily dosing of nebulized amikacin in an in vitro Hollow-Fiber Infection Model against 3 clinical isolates of Pseudomonas aeruginosa.
This study aims to compare the bacterial killing of once- versus twice-daily nebulized amikacin against Pseudomonas aeruginosa and to determine the optimal duration of therapy. Three clinical P. aeruginosa isolates (amikacin MICs 2, 8, and 64 mg/L) were exposed to simulated epithelial lining fluid exposures of nebulized amikacin with dosing regimens of 400 mg and 800 mg once- or twice-daily up to 7-days using the in vitro hollow-fiber infection model. Quantitative cultures were performed. Simulated amikacin dosing regimens of 400 mg twice-daily and 800 mg once-daily achieved ≥2-log reduction in the bacterial burden within the first 24-hours of therapy for all isolates tested. No dosing regimen suppressed the emergence of amikacin resistance. No difference in bacterial killing or regrowth was observed between 3- and 7-days of amikacin. Amikacin doses of 800 mg once-daily for up to 3-days may be considered for future clinical trials.
Topics: Aerosols; Amikacin; Anti-Bacterial Agents; Bacteriological Techniques; Drug Administration Schedule; Drug Resistance, Bacterial; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa
PubMed: 33714790
DOI: 10.1016/j.diagmicrobio.2021.115329 -
The Journal of Infectious Diseases Nov 1976During and after a 4-hr intravenous infusion of amikacin and kanamycin in a cross-over study in healthy adult male volunteers, average concentrations of drug in serum...
During and after a 4-hr intravenous infusion of amikacin and kanamycin in a cross-over study in healthy adult male volunteers, average concentrations of drug in serum were similar, with half-lives of approximately 2 hr. Apparent volumes of distribution at the steady state averaged 30% of body weight, and the rate of renal clearance was less than the rate of creatinine clearance (83 vs. 120 ml/min), a finding that indicates tubular reabsorption. The rate of serum clearance was greater than the rate of renal clearance (100 vs 83 ml/min). Urinary excretion in 24 hr averaged 94% of the dose, and there was no binding of serum proteins. In another cross-over study, volunteers received single intramuscular injections of these antibiotics. Peak concentrations of drug in serum after 45 min to 2 hr averaged 19.9 and 19.0 mug/ml for amikacin and kanamycin, respectively. Serum half-lives between 4 and 8 hr after administration of drug were 2 hr, and an average of 94% of the dose was recovered in the urine in 24 hr. Thus, the pharmacologic properties of amikacin and kanamycin were virtually identical.
Topics: Adult; Amikacin; Blood Proteins; Humans; Kanamycin; Male; Protein Binding
PubMed: 993624
DOI: 10.1093/infdis/135.supplement_2.s312 -
BMC Pharmacology & Toxicology Nov 2012The objectives of the current study were to determine amikacin pharmacokinetics in patients undergoing treatment with continuous venovenous haemodiafiltration (CVVHDF)... (Clinical Trial)
Clinical Trial
BACKGROUND
The objectives of the current study were to determine amikacin pharmacokinetics in patients undergoing treatment with continuous venovenous haemodiafiltration (CVVHDF) in an Intensive Care Unit (ICU), and to determine whether peak and trough concentration data could be used to predict pharmacokinetic parameters. An open prospective study was undertaken, comprising five critically ill patients with sepsis requiring CVVHDF.
METHODS
Peak and trough plasma concentrations and multiple serum levels in a dosage interval were measured and the latter fitted to both a one- and two-compartment model. Blood and ultrafiltrate samples were collected and assayed for amikacin to calculate the pharmacokinetic parameters; total body clearance (TBC), elimination rate constant (k) and volume of distribution (Vd). The concentration of amikacin in ultrafiltrate was used to determine the clearance via CVVHDF. CVVHDF was performed at prescribed dialysate rates of 1-2l h-1 and ultrafiltration rate of 2l h-1. Blood was pumped at 200ml/min using a Gambro blood pump and Hospal AN69HF haemofilter. Amikacin dosing was according to routine clinical practice in the Intensive Care Unit.
RESULTS
The multi serum level study indicated that the one compartment model was adequate to characterize the pharmacokinetics in these patients suggesting that peak and trough plasma level data may be used to estimate individual patient pharmacokinetic parameters and to optimise individual patient dosing during treatment with CVVHDF. CVVHDF resulted in an amikacin k of 0.109+/-0.025 h, t1/2 of 6.74 +/- 1.69h, TBC of 3.39+/-0.817 h-1, and Vd of 31.4 +/- 3.27. The mean clearance due to CVVHDF of 2.86 l h-1 is similar to the creatinine clearance of 2.74 +/-0.4 lh-1. Amikacin was significantly cleared by CVVHDF, and its half life in patients on CVVHDF was approximately 2-3 times that reported in subjects without renal impairment and not undergoing haemodiafiltration for any reason.
CONCLUSIONS
CVVHDF contributes significantly to total clearance of amikacin. The use of pharmacokinetic parameter estimates obtained from two steady state serum-drug concentrations (peak and trough) can be used to guide individualised dosing of critically ill patients treated with CVVHDF. This is considered a useful strategy in this patient cohort, particularly in avoiding the risk of underdosing.
Topics: Aged; Amikacin; Anti-Bacterial Agents; Critical Illness; Female; Hemodiafiltration; Humans; Male; Middle Aged; Models, Biological; Prospective Studies
PubMed: 23136834
DOI: 10.1186/2050-6511-13-14 -
Journal of Veterinary Pharmacology and... Apr 2008The purpose of the study was to compare the pharmacokinetics of amikacin administered i.v., to Greyhound and Beagle dogs and determine amikacin pharmacokinetics... (Comparative Study)
Comparative Study
The purpose of the study was to compare the pharmacokinetics of amikacin administered i.v., to Greyhound and Beagle dogs and determine amikacin pharmacokinetics administered subcutaneously to Greyhounds. Amikacin was administered i.v. at 10 mg/kg to six healthy Greyhounds and six healthy Beagles. The Greyhounds also received amikacin, 10 mg/kg s.c. Plasma was sampled at predetermined time points and amikacin concentrations determined by a fluorescence polarization immunoassay (FPIA). The volume of distribution was significantly smaller in Greyhounds (mean = 176.5 mL/kg) compared to Beagles (234.0 mL/kg). The C(0) and AUC were significantly larger in Greyhounds (86.03 microg/mL and 79.97 h x microg/mL) compared to Beagles (69.97 microg/mL and 50.04 h x microg/mL). The plasma clearance was significantly lower in Greyhounds (2.08 mL/min/kg) compared to Beagles (3.33 mL/min/kg). The fraction of the dose absorbed after s.c. administration to Greyhounds was 0.91, the mean absorption time was 0.87 h, and the mean maximum plasma concentration was 27.40 microg/mL at 0.64 h. Significant differences in the pharmacokinetics of amikacin in Greyhounds indicate it should be administered at a lower dose compared to Beagles. The dose in Greyhounds to achieve a C(max):AUC >or= 8 for bacteria (with an MIC
Topics: Amikacin; Animals; Anti-Bacterial Agents; Area Under Curve; Dogs; Female; Injections, Intravenous; Injections, Subcutaneous; Male; Pedigree
PubMed: 18307501
DOI: 10.1111/j.1365-2885.2008.00938.x -
Developmental Pharmacology and... 198417 children with serious infections were treated for an average period of 9.5 days with 420 mg/m2/dose of amikacin every 8 h. The nephrotoxicity and ototoxicity of this...
17 children with serious infections were treated for an average period of 9.5 days with 420 mg/m2/dose of amikacin every 8 h. The nephrotoxicity and ototoxicity of this 'high-dose' regimen was studied. None of the children had evidence of nephrotoxicity. Of 9 children who could be clearly evaluated, 1 child experienced a delayed transient auditory dysfunction. 1 child experienced delayed serious deafness, but was receiving other ototoxic drugs. Despite the fact that the doses averaged 54.1 mg/kg/day, 5 children in our series had peak concentrations lower than that recommended for adults with serious infection.
Topics: Adolescent; Amikacin; Bacterial Infections; Child; Child, Preschool; Creatinine; Deafness; Hearing; Hearing Loss, Bilateral; Humans; Infant; Kanamycin; Kidney; Time Factors
PubMed: 6518944
DOI: 10.1159/000457188