Peak Serum Gentamicin Concentrations Research Articles

Gentamicin concentration and acute kidney injury in term neonates treated for neonatal sepsis with gentamicin and ampicillin-cloxacillin combination.

Gentamicin is widely used to treat neonatal infections caused by both Gram-negative and Gram-positive bacteria, and the WHO recommends its use while monitoring serum creatinine and gentamicin concentrations to avoid drug-induced nephrotoxicity and ototoxicity. Yet in some resource-limited settings, the drug is used without monitoring. A population pharmacokinetics study involving term neonates with neonatal infection admitted to a neonatal unit. Participants were started on intravenous gentamicin 5 mg/kg once a day in combination with ampicilin-cloxacillin. Blood samples for serum gentamicin concentration were taken at 0.25, 0.5, 1, 2, 3, 5, 6, 8, 10, 12, 14, 16, 18, 20, 23, and 24 hours after the initial dose, each participant contributing two samples to the 24 hour sampling schedule. An additional sample for trough concentration was taken from each participant just before the third gentamicin dose while serum creatinine concentration was measured before and after treatment. Twenty-four participants were enrolled into the study and included in the final analysis. Mean (SD) peak and trough serum gentamicin concentrations were 16.66 (0.64) µg/mL and 3.28 (0.70) µg/mL, respectively. Gentamicin clearance (CL) was 0.40 mL min-1 kg-1 and volume of distribution (VD) was 0.31 L kg-1. Mean (SD) serum creatinine level after treatment was 209.7 (70.4) µmol/L compared to 103.3 (23.6) µmol/L before treatment [mean difference (106.4 ± 67.1; 95% confidence interval (CI): 78.1; 134.7 µmol/L; t (23) = 7.77; P < 0.001]. All participants fulfilled the Kidney Disease Improving Global Outcomes (KDIGO) criteria for acute kidney injury after treatment. Treatment of neonatal infection with antimicrobial regimen containing gentamicin, without renal function and gentamicin concentration monitoring, carries a significant risk for drug-induced acute kidney injury.

An evaluation of serum gentamicin concentrations and bacterial susceptibility to gentamicin in equine practice.

BackgroundTherapeutic drug monitoring and minimum inhibitory concentration (MIC) data allow more informed use of gentamicin.Hypothesis/ObjectivesTo measure peak and trough serum gentamicin concentrations in horses after a 6.6 mg/kg dose of gentamicin given IV and the MIC of gentamicin of bacteria for which gentamicin might be selected.MethodsRetrospective analysis of hospital records. Peak and trough plasma gentamicin concentrations were measured after 6.6 mg/kg gentamicin IV in 339 hospitalized horses. The MIC of gentamicin was measured for 503 isolates from ambulatory practice and 33 from hospital practice. The distribution of gentamicin concentrations and MIC results were compared to current recommendations for MIC breakpoints.ResultsThe median serum gentamicin concentration at 60 minutes after administration (C 60min) was 21.4 μg/mL with a distribution indicating that bacteria with MIC ≥2 μg/mL were unlikely to be exposed to sufficient gentamicin for effective killing. Approximately 90% of isolates from ambulatory practice and 36% of hospital isolates had MICs at or below breakpoints for susceptibility with most of the remainder unlikely to be responsive, even to higher IV doses.Conclusions and Clinical ImportanceGentamicin at a dosage of 6.6 mg/kg IV is likely to be effective against the majority of infections encountered in ambulatory practice, but less effective in an equine hospital. Because there was a dichotomy of most bacteria as being clearly susceptible or clearly resistant to gentamicin, it appears unlikely that higher doses would have been more efficacious, especially in the hospitalized population in our study.

Illustrative neonatal cases regarding drug delivery issues.

Illustrative neonatal cases regarding drug delivery issues.

Predictive performance of gentamicin dosing nomograms

BackgroundSeveral nomograms have been proposed to facilitate the determination of initial gentamicin dosing regimens in clinical settings. This study aimed to assess the predictive performance of these nomograms in Korean patients.MethodsGentamicin concentrations were determined in 84 patients with infective endocarditis (IE) and in 95 patients with other infections. All patients underwent therapeutic drug monitoring in Seoul National University Hospital from 2006 to 2012. Individual pharmacokinetic parameters were estimated using a Bayesian method, which predicted steady state peak and trough serum concentrations. Six nomograms were evaluated in patients with “other” infections: the Thomson guidelines, Hull-Sarubbi table, and Rule of Eights, for multiple daily dosing; and the Hartford nomogram, Barnes-Jewish Hospital nomogram, and Sanford Guide, for extended-interval dosing. In IE patients, synergistic combination dosing nomograms, based on the American Heart Association dosing interval guidelines, were evaluated.ResultsGentamicin dosing nomograms performed poorly in attaining the target peak serum concentrations. Multiple-daily dosing nomograms predicted peak serum gentamicin concentrations better than did the extended-interval dosing nomograms (31.9%–72.3% vs 4.3%–45.7%, respectively). Similarly, in patients with IE, the once-daily dosing nomogram resulted in a significantly lower percentage of patients achieving target peak gentamicin concentrations than that associated with the thrice-daily dosing nomogram (P=0.0015). All of the multiple-daily dosing, extended-interval dosing, and synergistic combination dosing nomograms predicted the nontoxic target trough concentrations in >80% of patients.ConclusionGentamicin dosing nomograms performed poorly in achieving the target peak serum concentrations. New gentamicin nomograms may be required in patients with IE, particularly for once-daily dosing. Therapeutic drug monitoring is highly recommended for gentamicin to ensure that the target concentrations are achieved.

Impact of small‐for‐gestational age (SGA) status on gentamicin pharmacokinetics in neonates

We compared gentamicin pharmacokinetics among neonates born small-for-gestational age (SGA) and appropriate for gestational age (AGA). We further compared gentamicin pharmacokinetics in subgroups of AGA and SGA neonates born preterm and term and treated within and after the initial week of age. Steady state peak and trough serum gentamicin concentrations were used to calculate clearance (Cl), elimination constant (Kel), volume of distribution (Vd), and half-life (t1/2 ) in infants (n = 236) who received ≥48 hours therapy. Statistical analyses (SPSS 17.0) included chi-square and the non-parametric Mann-Whitney U-test. SGA infants treated early (≤7days) (n = 29) and at postmenstrual ages ≤32 weeks (n = 23) had significantly lower median Kel (0.069/h vs. 0.081/h and 0.067/h vs. 0.075/h) and clearance (0.58 mL/kg/min vs. 0.68 mL/kg/min and 0.46 mL/kg/min vs. 0.65 mL/kg/min), compared to those born AGA. There were no significant differences in pharmacokinetic profiles with later therapy or at more mature ages. The prolonged half-life of gentamicin may need to be considered in dosing regimens for preterm SGA infants in the initial week of life.

The effect of postnatal age on gentamicin pharmacokinetics in neonates.

To determine if gentamicin serum concentrations obtained from newborns on day 2 of life versus days 3-4 yield significantly different pharmacokinetic parameter values. Retrospective chart review. Neonatal intensive care unit. Two hundred and sixty-seven infants who had peak and trough gentamicin serum concentrations determined on days 2, 3, or 4 of life. Determination of peak and trough serum gentamicin concentrations on days 2, 3, or 4 of life. The elimination rate constant, serum half-life, volume of distribution, and clearance of gentamicin were calculated using a one-compartment pharmacokinetic model. Gestational age, birthweight, gentamicin dosage, peak and trough gentamicin concentrations, and hours after birth at which serum concentrations were drawn were recorded for all infants. Infants were stratified into three groups based on gestational age: 28 weeks or younger, older than 28 weeks but younger than 37 weeks, and 37 weeks or older. Birthweight and calculated pharmacokinetic parameters were compared by 2-tailed Student t test to determine if significant differences existed between pharmacokinetics parameters determined on day 2 of life versus days 3 or 4 within each of the gestational age groups. These analyses revealed only one significant difference between parameters assessed on day 2 versus days 3 or 4: at day 2, the mean trough concentration of gentamicin in infants of gestational age between 28 and 37 weeks was 1.63 +/- 0.44 mg/L, whereas at days 3 or 4, the same parameter for patients of the same gestational age was 1.4 +/- 0.48 mg/L (p=0.005). With one exception--elevated trough concentrations in infants in the gestational age group between 28 and 37 weeks--pharmacokinetic parameters calculated using gentamicin serum concentrations determined on day 2 of life are not significantly different from those derived from gentamicin serum concentrations determined on days 3 or 4. This suggests that gentamicin serum concentrations and subsequent dosage adjustments can be determined on day 2 of life.

Bayesian Pharmacokinetic Analysis of a Gentamicin Nomogram in Neonates: A Retrospective Study

Background: Although gentamicin is used extensively within the first week of life for suspected sepsis in neonates, little is known about the performance of gentamicin dosing nomograms in this population. Objective: The goal of our study was to retrospectively assess the performance of a gentamicin dosing nomogram in neonates given gentamicin during the first week after birth. Methods: In this retrospective study, gentamicin therapeutic drug monitoring data were collected during routine clinical care for all neonates who were born in St. Boniface General Hospital (Winnipeg, Manitoba, Canada) between January 1999 and April 2001 and given gentamicin during the first week after birth. We used Bayesian pharmacokinetic analysis to retrospectively assess the performance of our gentamicin dosing nomogram in neonates born at gestation ages <32 weeks, between 32 and 34 weeks, and >34 weeks. Bayesian pharmacokinetic values for parameters within groups were compared and used to explore predicted peak and trough serum gentamicin concentrations based on the institutional dosing nomogram. Results: In a total of 58 neonates, those neonates born at ≤34 weeks' gestation had a weight-normalized apparent volume of gentamicin distribution 1.6 times larger than infants born after 34 weeks' gestation ( P<0.001), as identified by Bayesian analysis. Weight-normalized gentamicin clearance was 22% lower in the youngest age category ( P<0.01). Only 33% of predicted peak serum gentamicin concentrations were >6 mg/L for neonates born at ≤34 weeks' gestation, whereas 90% were therapeutic in neonates born at >34 weeks' gestation ( P<0.001). With the present nomogram, the likelihood of an indication for adjustment of the dosing regimen was 12.4-fold higher (95% CI, 3.5–43.7) for those neonates born at ≤34 weeks' gestation. Conclusions: These results have important clinical implications with regard to the advisability of determining peak serum gentamicin concentrations in neonates born at ≤34 weeks' gestation. Sampling of peak serum concentrations is indicated in this population to avoid underdosing and potential loss of therapeutic efficacy.

Gentamicina en dosis única diaria frente a tres dosis diarias en lactantes con pielonefritis aguda

Once-daily dosing (ODD) of gentamicin is advocated as an effective and safe treatment of Gram-negative bacterial infections in adults. There are insufficient data in the literature to justify its use in infants. To compare the efficacy of ODD of gentamicin with that of classical thrice-daily (t.i.d.) administration in infants with acute pyelonephritis. We performed a quasi-experimental study comparing 33 infants who received ODD of gentamicin with a historical control group of 25 infants treated with gentamicin t.i.d. Leukocytosis, C-reactive protein, creatinine, gentamicin dose, peak and trough values, time required for disappearance of fever, and outcome were analyzed. The mean doses of gentamicin (mg/kg/day) were higher in the t.i.d. group (6.4 1.14) than in the ODD group (5.06 0.22; p < 0.001). Peak serum gentamicin concentrations (micro g/ml) were significantly higher in the ODD group (9.32 1.4) than in the t.i.d. group (5.09 1.15; p < 0.001). Mean trough gentamicin concentrations (micro g/ml) were lower in the ODD group than in the t.i.d. group (0.23 0.26 vs 0.78 0.45; p 0.001). There were no significant differences in the duration of fever between the groups (30.64 32 hours in the t.i.d. group vs. 28.57 32 hours in the ODD group). Serum creatinine levels were normal during treatment in both groups. In all patients outcome was good and no adverse effects were noted. Treatment with ODD of gentamicin in our population of infants with acute pyelonephritis was as effective as traditional administration t.i.d. and possibly was equally safe or safer.

Once daily dosing of gentamicin in infants and children

Aminoglycosides are frequently used in children. The standard daily dosing (SDD) in infants and children is twice or three times daily depending on age. The aim of this paper is to review the current data regarding the safety and effectiveness of once daily dosing (ODD) of gentamicin in children. A Medline search was conducted for comparison studies between ODD and SDD of gentamicin in children in term of pharmacokinetic indices and toxicity. Overall 13 studies describing ODD of gentamicin in children were found suitable for this review. In most studies steady state peak serum gentamicin concentrations were significantly higher in the ODD groups. Steady state trough concentrations >2 microg/ml were documented in 5 to 55% of patients treated with the SDD as compared with 0 to 24% in the ODD groups. The mode of dosing did not affect the volume of distribution; however, the t1/2 was significantly longer in the ODD groups. ODD was found to be cost-saving. In a few studies the efficacy of ODD was similar to that of SDD. These studies suggest that ODD compared with SDD of gentamicin is theoretically more efficacious and has no higher toxicity at 48 to 96 h in neonates and at 3 to 10 days of therapy in older infants and children.

Targeting Gentamicin Concentrations in Babies: The Younger the Baby, the Larger the Loading Dose and the Longer the Dose Interval

To improve therapeutic range targeting of serum gentamicin concentrations in the newborn.

Pharmacokinetics of single daily dose gentamicin in children with cancer.

To study the pharmacokinetics of single daily dose (SDD) gentamicin in children with cancer. Serum concentrations of gentamicin were prospectively measured at 0.5, 8, 16, and 24 hours after a single daily dose of gentamicin 6 mg/kg, given as a 30-minute infusion in 18 febrile children with cancer and a central venous catheter. Then the peak (0.5-hour) and 12-hour serum concentrations of gentamicin were prospectively measured after a SDD of 7 mg/kg during 73 febrile episodes in 54 pediatric cancer patients with suspected infections. The aim was to achieve a peak serum concentration of 15 to 20 microg/mL 10 times the minimum inhibitory concentration (MIC) for sensitive Pseudomonas strains, resulting in good bactericidal activity and a long post-antibiotic effect (PAE) after a SDD of gentamicin. The mean serum peak gentamicin concentration 30 minutes after the end of the infusion of 6 mg/kg was 13.3 +/- 4.0 microg/mL. The mean serum concentration 16 hours after the infusion was 0.3 +/- 0.2 microg/mL. The mean peak and 12-hour serum concentration after SDD of 7 mg/kg was 17.2 +/- 3.9 microg/mL and 0.9 +/- 0.7 microg/mL, respectively. The mean peak serum concentration after SDD of 7 mg/kg in children younger than 5 years of age (16.1 +/- 3.5 microg/mL ) was significantly lower than that of children over 5 years of age (18.2 +/- 3.9 microg/mL; P = 0.02). The desired peak serum concentration was achieved in 67% of children younger and 84% of those older than 5 years of age. Adequate peak serum concentrations of gentamicin in children may be obtained with a SDD of 7 mg/kg. Children younger than 5 years of age achieve lower peak serum gentamicin concentration after SDD of 7 mg/kg than those older than 5 years.

Population pharmacokinetics of gentamicin in patients with cancer.

The purpose of this study was to describe the population pharmacokinetics of gentamicin in patients with cancer, to identify possible relationships between clinical covariates and population pharmacokinetic parameter estimates and to examine the relevance of existing dosage nomograms in light of the population model developed in these patients. Data were collected prospectively from 210 patients with cancer and were analysed with package NONMEM. Data were split into two sets: a population data set and an evaluation set. Creatinine clearance was estimated using measured creatinine concentrations and using 'low' creatinines set to a minimum of 60 micromol l(-1), 70 micromol l(-1) or 88.4 micromol l(-1) A two compartment model was fitted to the concentration-time curve. Two best models were obtained, one that related clearance to estimated creatinine clearance (minimum creatinine value 60 micromol l(-1)) and the other that related clearance to age, creatinine concentration and body surface area. Volume of the central compartment was influenced by body surface area and albumin concentration. For both models 90% of measured concentrations lay within the 95% confidence interval of the simulated concentrations and the mean prediction errors were -7.2% and -6.6%, respectively. A final analysis performed in all patients identified the following relationship CL (1 h(-1))=0.88 x (1 + 0.043 x creatinine clearance) and central volume of distribution V1 (1)=8.59 x body surface area x (albumin/34)(-0.39). The mean population estimate of intercompartmental clearance (Q) was 1.301 h(-1) and peripheral volume of distribution (V2) was 9.801. Coefficient of variation was 18.5% on clearance and 28.2% on Q. Residual error expressed as a standard deviation was 0.36 mg l(-1) at 1.0 mg l(-1) and 1.32 mg l(-1) at 8.0 mg l(-1). The mean population estimate of clearance was 4.21 h(-1) and volume of distribution (Vss) was 24.61 (0.381 kg(-1)). The mean population estimates of half-lives were 1.8 h and 8.0 h. In the context of published nomograms this analysis indicated that both the traditional approach and the new, 'once daily' approach should achieve satisfactory concentrations in cancer patients although serum concentration monitoring is required to confirm optimal dosing in individual patients.

Single intravenous and multiple dose pharmacokinetics of gentamicin in healthy llamas

Objective To determine the pharmacokinetics of gentamicin sulfate in healthy llamas after IV administration of a single bolus and after repeated parenteral administration. Design Prospective clinical trial. Animals 19 clinically normal, adult male llamas for the single-dose trial and 10 of the 19 llamas for the multiple-dose trial. Procedure In the first trial, llamas were given gentamicin (5 mg/kg of body weight, IV) as a single bolus, and serum gentamicin concentration was monitored over the next 48 hours. 2 months later, llamas were given gentamicin (2.5 mg/kg) IV for the first day, then IM every 8 hours for 7 days. Serum gentamicin concentration and indices of renal function and damage were monitored during the 7 days. Results There were no significant dose- or time-related differences in clearance of the drug; volume of distribution; apparent coefficients of the distribution and elimination phases, α and β, respectively; mean residence time; or distribution (t½α) and elimination phase (tt/2β) half-lives. The 5 mg/kg IV kinetic study revealed t½β, of 14.5 ± 5.06 minutes and t½β of 166 ± 20.5 minutes. The 2.5 mg/kg IV kinetic study revealed t½α of 17.7 ± 6.59 minutes and t½β of 165 ± 40.3 minutes. Peak serum gentamicin concentration averaged 10.10 μg/ml in the multiple-dose trial, and trough concentration averaged 1.50 μg/ml. Conclusions Dose effects were not observed for gentamicin clearance, volume of distribution, or half-lives. Multiple dosing at 2.5 mg/kg every 8 hours does not appear to cause renal impairment in healthy llamas. Clinical Relevance Gentamicin pharmacokinetic variables in llamas appear to resemble those in other ruminant species. (Am J Vet Res 1996;57:1193–1199)

Neural network predicted peak and trough gentamicin concentrations.

Predictions of steady state peak and trough serum gentamicin concentrations were compared between a traditional population kinetic method using the computer program NONMEM to an empirical approach using neural networks. Predictions were made in 111 patients with peak concentrations between 2.5 and 6.0 micrograms/ml using the patient factors age, height, weight, dose, dose interval, body surface area, serum creatinine, and creatinine clearance. Predictions were also made on 33 observations that were outside the 2.5 and 6.0 micrograms/ml range. Neural networks made peak serum concentration predictions within the 2.5-6.0 micrograms/ml range with statistically less bias and comparable precision with paired NONMEM predictions. Trough serum concentration predictions were similar using both neural networks and NONMEM. The prediction error for peak serum concentrations averaged 16.5% for the neural networks and 18.6% for NONMEM. Average prediction errors for serum trough concentrations were 48.3% for neural networks and 59.0% for NONMEM. NONMEM provided numerically more precise and less biased predictions when extrapolating outside the 2.5 and 6.0 micrograms/ml range. The observed peak serum concentration distribution was multimodal and the neural network reproduced this distribution with less difference between the actual distribution and the predicted distribution than NONMEM. It is concluded that neural networks can predict serum drug concentrations of gentamicin. Neural networks may be useful in predicting the clinical pharmacokinetics of drugs.

Prediction of Gentamicin Concentrations in Neonates and Infants Using a Bayesian Pharmacokinetic Model

This study retrospectively characterized population-based pharmacokinetic parameters for gentamicin in neonates and young infants, and evaluated the predictive performance of these parameters in a Bayesian forecasting program. Population parameter estimates were determined from the serum concentration-time data of 19 neonates and infants using a one-compartment open infusion model and nonlinear least-squares regression analysis. Univariate and multiple stepwise linear regression analyses were used to determine significant relationships between demographic characteristics and gentamicin pharmacokinetic parameters. Creatinine clearance and postnatal age were the most significant predictors of weight-standardized gentamicin clearance (model r2 = 0.86). The relationships between patient characteristics and population-based parameters were incorporated into the one-compartment Bayesian forecasting model. A second group of 17 neonates and infants receiving 35 courses of gentamicin therapy were used to evaluate the predictive performance of the population-based parameters and a Bayesian forecasting model. The population parameters provided accurate prediction of steady state gentamicin concentrations throughout multiple courses of therapy within the same patient. Bayesian forecasting further minimized the mean prediction error (bias) once a set of steady state peak and trough serum gentamicin concentrations became available (peak concentrations: -0.062 vs. -0.273 mg/l; trough concentrations: -0.006 vs. -0.161 mg/l). The mean absolute error (accuracy) was similar for the two sets of parameters. The observed accuracy of both the population parameters and Bayesian forecasting suggests that monitoring of serum gentamicin concentrations can be kept to minimum in neonates and infants.

Gentamicin pharmacokinetics, nephrotoxicity, and prediction of mortality in febrile neutropenic patients.

The pharmacokinetics of gentamicin in 34 febrile neutropenic patients (40 courses) were compared with those in 40 nonneutropenic patients receiving the drug. No pharmacokinetic differences were seen in half-life, volume of distribution (liter per kilogram; total and ideal body weight), or clearance (milliliter per minute per 1.73 m2). The incidences of nephrotoxicity in the two groups were not statistically different. Because of the small number of patients with positive cultures, no relationship between initial peak serum gentamicin concentration and mortality could be determined. Mortality risk factors that were determined to be statistically important included presence of pneumonia, persistent fever in the presence of anti-infective therapy of more than 1 week duration, and peak serum creatinine of greater than 1.2 mg/dl. Initial aminoglycoside dosing in the febrile neutropenic patient should be similar to that in the nonneutropenic patient, with concentrations in serum monitored and doses adjusted accordingly.

Comparison of serum and renal gentamicin concentrations with fractional urinary excretion tests as indicators of nephrotoxicity

Gentamicin was given to six sheep at a dosage rate of 80 mg/kg/day divided into three daily doses to cause nephrotoxicity. Peak serum gentamicin concentrations rose significantly throughout dosing (P less than 0.05), but trough serum gentamicin concentrations increased dramatically (P less than 0.01) from initial concentrations of 3.2-9.1 micrograms/ml to final trough concentrations of 31.5-195 micrograms/ml by 6-10 days on gentamicin. The serum gentamicin elimination half-life (t1/2) was doubled in each animal by approximately 6 days on therapy, with the sheep that were the most clinically affected by the nephrotoxic effects of gentamicin showing increases in t1/2 earlier than those sheep that remained less intoxicated. These changes occurred before many other clinical indicators of nephrotoxicity, with only urinary enzyme excretions preceding the changes in gentamicin elimination. Thus, alterations in the elimination of gentamicin may be one of the first clinical indicators of the occurrence of gentamicin-induced nephrotoxicity.

Comparison of a Bayesian Program with Three Microcomputer Programs for Predicting Gentamicin Concentrations

A recently developed Bayesian regression program was compared with three other aminoglycoside pharmacokinetic dosing programs available for clinical use. From 30 adult patients, 152 measured serum gentamicin concentrations (SGC) were evaluated retrospectively (78 peak and 74 trough). Predictive performance was compared for each method by using the first peak and trough SGC pair to predict subsequent serum concentrations, making a total of 92 predictions (48 peak and 44 trough). The two Bayesian programs (Brater and Koup) were further evaluated using only one initial peak or trough SGC to make the same predictions. Mean predicted error (ME), mean absolute error (MAE), and root mean squared error (RMSE) were calculated for each method. Prediction bias and precision were compared statistically, between each method, by calculating the 95% confidence intervals for the delta ME and delta MAE, respectively. No statistically significant differences were found in the MAEs among any of the methods for predicting peak SGCs, with the exception of the Brater program, using a single trough SGC, which was statistically less precise (less than 0.05). There were few statistically significant differences in the MAEs for trough SGCs; however, Koup's Bayesian program using a single trough concentration yielded statistically more precise predictions than the other methods. The ME was found to differ significantly (p less than 0.05) among estimates for peak and trough SGCs provided by some of the predictive methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics and antibacterial activity of two gentamicin products given intramuscularly

The pharmacokinetics and antibacterial activity of two injectable gentamicin products given i.m. were compared. Ten healthy men randomly received either Schering or Invenex gentamicin 1 mg/kg (as the sulfate salt) by intramuscular injection into the deltoid muscle. Four to six weeks later, subjects received the alternate preparation at the same dose in the opposite arm. Blood samples for gentamicin concentrations were obtained before drug administration and at various times for up to four hours after drug administration; urine from each subject was also collected before and after drug administration. Values for area under the curve, elimination rate constant, peak serum gentamicin concentration and time to peak concentration, clearance, half-life, and percentage of drug excreted in the urine over four hours were compared for each preparation in each subject. The serum inhibitory and bactericidal activities of each gentamicin preparation against Escherichia coli and Klebsiella pneumoniae were also evaluated. None of the pharmacokinetic values for the two preparations was significantly different. The inhibitory and bactericidal activities resulting from each product were also comparable and adequate. No clinically important differences in pharmacokinetic behavior or inhibitory or bactericidal activity were found between gentamicin products of Schering and Invenex.

GENTAMICIN IN PREMATURE NEONATES: A DOSAGE REGIMEN BASED ON MATURITY

Gentamicin toxicity and efficacy studies have indicated desired peak and trough serum concentrations of 4-12 mcg/ml and less than 2 mcg/ml, respectively. Choosing an appropriate dose and dosage interval for premature infants is complicated by decreasing glomerular function with decreasing gestational age. We tested a regimen in which 24 infants less than 7 days of age,who were born between 26 and 36 weeks of gestation, received 2.5 mg/kg of gentamicin intravascularly every 18 hours. Trough serum gentamicin concentrations exceeded 2 mcg/ml in 33%; peak serum concentrations exceeded 12 mcg/ml in none but were less than 4 mcg/ml in 12.5%. Regression analysis of the data revealed inverse linear correlations between peak and trough serum gentamicin concentrations and gestational age (p<0.01 and p<0.05, respectively). Using these relationships a mathematical model was derived for calculating optimal gentamicin dose and dosage interval based on gestational age (G, in weeks):Initial dose (mg/kg) ė 4.2 + 0.038 GSubsequent doses (mg/kg) ė 3.4 + 0.031 GDosage interval (hours) ė 50 − 0.76 GThis regimen is designed to yield peak and trough serum concentrations of 8 mcg/ml and 1.5 mcg/ml, respectively. We conclude that the observed variations in gentamicin serum concentrations in premature neonates warrants the use of dosage regimens based on estimated gestational age. Additional clinical experience is needed to confirm the validity of these dosage recommendations.