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Paediatric Drugs Jun 2018Our objective was to determine the population pharmacokinetic parameters of amikacin in pediatric patients to contribute to the future development of a revised optimum...
OBJECTIVE
Our objective was to determine the population pharmacokinetic parameters of amikacin in pediatric patients to contribute to the future development of a revised optimum dose and population-specific dosing regimens.
METHODS
We performed a retrospective chart review in non-critical pediatric patients (aged 1-12 years) who received amikacin for suspected or proven Gram-negative infection at a university hospital. The population pharmacokinetic models were developed using Monolix 4.4. Pharmacokinetic/pharmacodynamic (PK/PD) simulations were performed to explore the ability of different dosage regimens to achieve the pharmacodynamic targets.
RESULTS
The analysis included 134 amikacin plasma concentrations from 67 patients with a mean ± standard deviation age of 4.1 ± 3.9 years and bodyweight of 15 ± 8.4 kg. The patients received an amikacin total daily dose (TDD) of 23 ± 7.3 mg/kg, which resulted in peak and trough concentrations of 20.65 ± 7.6 and 2.4 ± 1.7 mg/l, respectively. The estimated pharmacokinetic parameters for amikacin were 1.2 l/h and 6.5 l for total body clearance (CL) and the volume of distribution (V), respectively. Dosing simulations showed that the standard dosing regimen (15 mg/kg/day) of amikacin achieved the PK/PD target of peak serum concentration (C)/minimum inhibitory concentration (MIC) ≥ 8 for an MIC of 2 mg/l; higher doses were required to achieve higher MIC values.
CONCLUSION
The simulation results indicated that amikacin 20 mg/kg once daily provided a higher probability of target attainment with lower toxicity than dosing three times daily. In addition, combination therapy is recommended for pathogens with an MIC of ≥ 8 mg/l.
Topics: Amikacin; Anti-Bacterial Agents; Child; Child, Preschool; Drug Dosage Calculations; Female; Humans; Infant; Male; Retrospective Studies
PubMed: 29569124
DOI: 10.1007/s40272-018-0288-y -
International Journal of Clinical... Oct 1979
Clinical Trial
Topics: Aged; Amikacin; Clinical Trials as Topic; Double-Blind Method; Female; Gentamicins; Glomerular Filtration Rate; Humans; Kanamycin; Kinetics; Male; Pyelonephritis
PubMed: 387619
DOI: No ID Found -
Antimicrobial Agents and Chemotherapy Feb 1988The pharmacokinetics of amikacin were investigated in five stable patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Each patient was studied after...
The pharmacokinetics of amikacin were investigated in five stable patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Each patient was studied after the administration of 7.5 mg of amikacin per kg by both the intravenous (i.v.) and intraperitoneal (i.p.) route, allowing a 1-month washout period between doses. No differences in amikacin half-life, volume of distribution, total body clearance, or time-averaged peritoneal clearance were noted between the two routes of administration. After a 5-h dwell period, bioavailability as calculated by the area under the curve for i.p. amikacin was 53 +/- 14.0%. Amikacin pharmacokinetics parallel those of other aminoglycosides in CAPD patients when the drug is administered either i.v. or i.p. Single loading doses of amikacin administered i.v. to uninfected CAPD patients provided therapeutic serum and dialysate levels for many aerobic gram-negative organisms for up to 72 h. Because of the variability of absorption of i.p. administered amikacin, single i.p. doses are not recommended.
Topics: Absorption; Adult; Amikacin; Biological Availability; Female; Humans; Infusions, Intravenous; Infusions, Parenteral; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory
PubMed: 3364945
DOI: 10.1128/AAC.32.2.236 -
Antimicrobial Agents and Chemotherapy Apr 2020The aim of this work was to evaluate the pharmacokinetics of amikacin in Mexican patients with different renal functions receiving once-daily dosing regimens and the...
The aim of this work was to evaluate the pharmacokinetics of amikacin in Mexican patients with different renal functions receiving once-daily dosing regimens and the influence of clinical and demographical covariates that may influence the optimization of this antibiotic. A prospective study was performed in a total of 63 patients with at least one determination of amikacin plasma concentration. Population pharmacokinetic (PK) parameters were estimated by nonlinear mixed-effects modeling; validations were performed for dosing recommendation purposes based on PK/pharmacodynamic simulations. The concentration-versus-time data were best described by a one-compartment open model with proportional interindividual variability associated with amikacin clearance (CL) and volume of distribution (); residual error followed a homoscedastic trend. Creatinine clearance (CL) and ideal body weight (IBW) demonstrated significant influence on amikacin CL and , respectively. The final model [CL (liters/h) = 7.1 × (CL/130) and (liters) = 20.3 × (IBW/68)] showed a mean prediction error of 0.11 mg/liter (95% confidence interval, -3.34, 3.55) in the validation performed in a different group of patients with similar characteristics. There is a wide variability in amikacin PK parameters in Mexican patients. This leads to inadequate dosing regimens, especially in patients with augmented renal clearance (CL of >130 ml/min). Optimization based on the final population PK model in Mexican patients may be useful, since reliability and clinical applicability have been demonstrated in this study.
Topics: Adolescent; Adult; Aged; Amikacin; Anti-Bacterial Agents; Drug Elimination Routes; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Kidney; Kidney Function Tests; Male; Mexico; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Young Adult
PubMed: 32041715
DOI: 10.1128/AAC.02178-19 -
American Journal of Hospital Pharmacy Apr 1980The pharmacokinetics of single-dose amikacin sulfate was studied in seven morbidly obese patients to determine the fraction of fat weight (FW) that, when added to ideal...
The pharmacokinetics of single-dose amikacin sulfate was studied in seven morbidly obese patients to determine the fraction of fat weight (FW) that, when added to ideal body weight (IBW), will normalize the volume of distribution. Seven patients (mean total body weight of 166.5 kg) were each given a 1,250-g intravenous injection of amikacin. Amikacin serum levels over eight hours were measured by radioimmunoassay. A correction factor (CF) of 0.38 was found to normalize the patients' volume of distribution (Varea) to 0.26 liters/kg, when added to the patients' IBW. There was no significant difference between peak amikacin levels predicted using the actual Varea and using the Varea plus the CF. Predictions using the actual Varea and those using Varea estimated by ideal body weight were significantly different. In morbidly obese patients, peak amikacin serum levels can be predicted best when a volume of distribution based on IBW plus a correction factor of 38% of FW is used.
Topics: Adult; Amikacin; Body Weight; Female; Humans; Kanamycin; Kinetics; Male; Middle Aged; Models, Biological; Obesity
PubMed: 7377215
DOI: No ID Found -
Scandinavian Journal of Infectious... 1990Once-daily dosing of amikacin is a novel therapy regimen which seems pharmacokinetically appropriate for the primary group of patients considered for aminoglycoside... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Once-daily dosing of amikacin is a novel therapy regimen which seems pharmacokinetically appropriate for the primary group of patients considered for aminoglycoside therapy. In this study of 29 elderly patients with serious infections, amikacin 11 mg/kg or 15 mg/kg bw was administered as a short-term (30 min) intravenous infusion. The amikacin serum concentration-time profile was best described by a bi-exponential equation with a half-life of about 4.8 h. A triexponential equation was not applicable because the slow terminal elimination phase was not detected during the 24 h dosing interval. In practice, a uni-exponential equation is often used, and this may lead to incorrect conclusions about the elimination rate of amikacin. Amikacin clearance provides more direct information about elimination of amikacin than does serum half-life. Thus, there was a better correlation between the individual amikacin clearances and creatinine clearances (r = 0.89), than between the serum half-lives of amikacin and the creatinine clearances (r = 0.71). For elderly patients a smaller dose of amikacin than the regular daily dose of 15 mg/kg bw, i.e. about 11 mg/kg bw, seems recommendable, when it is given once daily. From the data obtained it is also obvious that once-daily dosing of amikacin does not eliminate the need for checking serum concentrations of the drug.
Topics: Aged; Amikacin; Creatinine; Drug Administration Schedule; Female; Half-Life; Humans; Infusions, Intravenous; Male; Middle Aged; Sepsis
PubMed: 2259867
DOI: 10.3109/00365549009027099 -
American Journal of Kidney Diseases :... Sep 1981A woman with subarachnoid hemorrhage inadvertently received 18 g of amikacin over a 4-hr period, 20 times the recommended total daily dose. Intravenous fluids were...
A woman with subarachnoid hemorrhage inadvertently received 18 g of amikacin over a 4-hr period, 20 times the recommended total daily dose. Intravenous fluids were administered to expedite renal excretion of the amikacin, and a peritoneal dialysis was performed to augment drug elimination. Drug levels were measured sequentially in serum, urine, and peritoneal dialysate. Renal clearance of the drug was increased compared to clearance following a standard dose and the drug was rapidly excreted in the urine. Amikacin was not detected in the peritoneal dialysate. There were no apparent toxic effects from the overdose. A patient with normal renal function who receives a potentially toxic dose of amikacin can be appropriately managed by careful hydration and maintenance of a generous diuresis.
Topics: Adult; Amikacin; Diuresis; Female; Humans; Kanamycin; Peritoneal Dialysis; Sodium Chloride
PubMed: 7332003
DOI: 10.1016/s0272-6386(81)80038-8 -
Journal of Chemotherapy (Florence,... Feb 2018This study aimed at investigating variables affecting amikacin pharmacokinetics in order to propose optimal initial dosing in critically ill adult patients treated with... (Observational Study)
Observational Study
This study aimed at investigating variables affecting amikacin pharmacokinetics in order to propose optimal initial dosing in critically ill adult patients treated with once-daily amikacin regimen. Amikacin pharmacokinetics was calculated based on plasma concentrations using one compartmental analysis. Relationships between pharmacokinetic parameters and demographic/clinical data were explored in linear regression models. Simulated dose and dosing intervals were derived from body size descriptors and estimated creatinine clearances for each patient. Amikacin volume of distribution best correlated with body surface area, while amikacin clearance was best predicted by CKD-EPI creatinine clearance. Our study suggests that dose of 517 mg per m of body surface area leads to amikacin levels most approaching target peak concentration. Dosing interval calculated as 228.7 × e + 15.84 most closely approximated optimal dosing intervals based on individual pharmacokinetics. The dosing nomogram based on CKD-EPI creatinine clearance was designed.
Topics: Aged; Amikacin; Anti-Bacterial Agents; Critical Illness; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged
PubMed: 28950787
DOI: 10.1080/1120009X.2017.1376818 -
The Journal of Antimicrobial... Nov 2022Annual mortality from neonatal sepsis is an estimated 430 000-680 000 infants globally, most of which occur in low- and middle-income countries (LMICs). The WHO...
BACKGROUND
Annual mortality from neonatal sepsis is an estimated 430 000-680 000 infants globally, most of which occur in low- and middle-income countries (LMICs). The WHO currently recommends a narrow-spectrum β-lactam (e.g. ampicillin) and gentamicin as first-line empirical therapy. However, available epidemiological data demonstrate high rates of resistance to both agents. Alternative empirical regimens are needed. Flomoxef and amikacin are two off-patent antibiotics with potential for use in this setting.
OBJECTIVES
To assess the pharmacodynamics of flomoxef and amikacin in combination.
METHODS
The pharmacodynamic interaction of flomoxef and amikacin was assessed in chequerboard assays and a 16-arm dose-ranged hollow-fibre infection model (HFIM) experiment. The combination was further assessed in HFIM experiments mimicking neonatal plasma exposures of clinically relevant doses of both drugs against five Enterobacterales isolates with a range of flomoxef/amikacin MICs.
RESULTS
Flomoxef and amikacin in combination were synergistic in bacterial killing in both assays and prevention of emergence of amikacin resistance in the HFIM. In the HFIM assessing neonatal-like drug exposures, the combination killed 3/5 strains to sterility, (including 2/5 that monotherapy with either drug failed to kill) and failed to kill the 2/5 strains with flomoxef MICs of 32 mg/L.
CONCLUSIONS
We conclude that the combination of flomoxef and amikacin is synergistic and is a potentially clinically effective regimen for the empirical treatment of neonatal sepsis in LMIC settings and is therefore suitable for further assessment in a clinical trial.
Topics: Infant; Infant, Newborn; Humans; Amikacin; Neonatal Sepsis; Cephalosporins; Microbial Sensitivity Tests; Anti-Bacterial Agents; Delivery of Health Care
PubMed: 36177766
DOI: 10.1093/jac/dkac323 -
The Journal of Antimicrobial... Sep 1979Twenty-two preterm infants of gestational age 26 to 34 weeks were treated with amikacin for suspected bacterial infection, using a dose of 7.5 mg/kg, 12-hourly, intra...
Twenty-two preterm infants of gestational age 26 to 34 weeks were treated with amikacin for suspected bacterial infection, using a dose of 7.5 mg/kg, 12-hourly, intra muscularly. Blood levels were measured using a radio-immunoassay kit capable of giving results within 4 h. One-hour peak levels showed wide variation and the mean level one hour after the first dose was 18.2 mg/1; in severe infections an initial loading dose of 10 mg/kg is therefore recommended. Trough levels in individual infants also varied considerably from day to day, but showed no overall accumulation. There was no obvious adverse effect on hepatic or renal function.
Topics: Amikacin; Bacterial Infections; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Newborn, Diseases; Kanamycin; Male; Radioimmunoassay
PubMed: 500515
DOI: 10.1093/jac/5.5.527