scholarly journals An Evaluation of Gentamicin, Tobramycin, and Amikacin Pharmacokinetic/Pharmacodynamic Parameters in HIV-Infected Children

2003 ◽  
Vol 8 (4) ◽  
pp. 274-283
Author(s):  
Juan Carlos Rodriguez ◽  
Steve Schoenike ◽  
Gwendolyn B. Scott ◽  
Maria T. Rossique-Gonzalez ◽  
Orlando Gomez-Marin
Keyword(s):  
Steady State ◽  
Inhibitory Concentration ◽  
Pharmacokinetic Parameters ◽  
Serum Concentrations ◽  
Klebsiella Species ◽  
Once Daily ◽  
Gram Negative ◽  
Trough Serum ◽  
Steady State Model ◽  
Dosing Method

BACKGROUND The purpose of the study was to calculate gentamicin, tobramycin, and amikacin pharmacokinetic parameters in HIV-infected children and compare conventional multiple daily aminoglycoside dosing to once-daily aminoglycoside (ODA) dosing in attaining peak serum aminoglycoside concentrations (SACs) to minimum inhibitory concentration for 90% of isolates (MIC90) ratios ≥8 against selected pathogens. METHODS Patients (<13yrs) receiving an aminoglycoside (15 patients/drug) in the treatment of gram-negative infection were studied. Intravenous gentamicin/ tobramycin were administered at a dose of 6–7.5 mg/kg/day and amikacin at 20–30 mg/kg/d divided every 8 hrs. Peak and trough serum concentrations were obtained and pharmacokinetic parameters were calculated utilizing a one-compartment steady-state model. SACs for gentamicin/tobramycin dosed at 7.5 mg/kg and amikacin at 22.5 mg/kg once daily were simulated using the calculated pharmacokinetic parameters. Peak SAC:MIC90 ratios were calculated for each dosing method. RESULTS Mean pharmacokinetic parameters were within 1 standard deviation of reported literature values. Mean peak:MIC90 ratio of ≥8 was attained only for Klebsiella species (MIC90 1 μg/mL) using conventional gentamicin/tobramycin dosing whereas mean amikacin peak:MIC90 ratios ≥8 were reached for Klebsiella, Enterobacter, and Citrobacter species (MIC90 4 μg/mL). ODA simulations predicted gentamicin/tobramycin peak:MIC90 ratios ≥8 in 100% of patients with an organism-MIC90 of 1 μcg/mL and in 80% of patients with an organism-MIC90 of 2 μg/mL. Amikacin peak:MIC90 ratio ≥8 was predicted for 93% of patients with an organism-MIC90 of 4 μg/mL but in only 27% if the MIC90 was 8 μg / mL. CONCLUSION Optimal peak SAC:MIC90 ratios using conventional aminoglycoside dosing were predicted only for organisms with low MIC90 values. ODA dosing represents an option for improving pharmacodynamic outcomes.

scholarly journals Achievement of Vancomycin Therapeutic Goals in Critically Ill Patients: Early Individualization May Be Beneficial

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Bita Shahrami ◽  
Farhad Najmeddin ◽  
Sarah Mousavi ◽  
Arezoo Ahmadi ◽  
Mohammad Reza Rouini ◽  
...  
Keyword(s):  
Steady State ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Pharmacokinetic Parameters ◽  
Serum Concentrations ◽  
Therapeutic Goals ◽  
Dose Monitoring ◽  
Trough Serum ◽  
Group 2 ◽  
Group 1

Objective.The aim of our study was to assess and validate the effectiveness of early dose adjustment of vancomycin based on first dose monitoring in achieving target recommended goal in critically ill patients.Methods.Twenty critically ill patients with sepsis received loading dose of 25 mg/kg of vancomycin and then were randomly assigned to 2 groups. Group 1 received maximum empirical doses of vancomycin of 15 mg/kg every 8 hrs. In group 2, the doses were individualized based on serum concentrations of vancomycin. First dose nonsteady state sampling was used to calculate pharmacokinetic parameters of the patients within 24 hours.Results.Steady state trough serum concentrations were significantly higher in group 2 in comparison with group 1 (19.4 ± 4.4 mg/L versus 14.4 ± 4.3 mg/L) (P=0.03). Steady state AUCs were significantly higher in group 2 compared with group 1 (665.9 ± 136.5 mg·hr/L versus 490.7 ± 101.1 mg·hr/L) (P=0.008).Conclusions.With early individualized dosing regimen, significantly more patients achieved peak and trough steady state concentrations. In the context of pharmacokinetic/pharmacodynamic goal of area under the time concentration curve to minimum inhibitory concentration (AUC/MIC) ≥400 and also to obtain trough serum concentration of vancomycin of ≥15 mg/L, it is necessary to individualize doses of vancomycin in critically ill patients.

scholarly journals Steady-State Plasma and Intrapulmonary Pharmacokinetics and Pharmacodynamics of Cethromycin

2004 ◽  
Vol 48 (9) ◽  
pp. 3508-3515 ◽  
Author(s):  
John E. Conte ◽  
Jeffrey A. Golden ◽  
Juliana Kipps ◽  
Elisabeth Zurlinden
Keyword(s):  
Steady State ◽  
Half Life ◽  
Dose Group ◽  
Drug Exposure ◽  
Pharmacokinetic Parameters ◽  
Multiple Time ◽  
Respiratory Pathogens ◽  
Once Daily ◽  
Standard Deviations ◽  
State Plasma

ABSTRACT The objective of this study was to determine the steady-state plasma and intrapulmonary pharmacokinetic parameters of orally administered cethromycin in healthy volunteers. The study design included administering 150 or 300 mg of cethromycin once daily to 25 or 35 healthy adult subjects, respectively, for a total of five doses. Standardized and timed bronchoalveolar lavage (BAL) was performed after the last dose. Blood was obtained for drug assay prior to the first and last dose, at multiple time points following the last dose, and at the time of BAL. Cethromycin was measured in plasma, BAL, and alveolar cell (AC) by using a combined high-performance liquid chromatography-mass spectrometric technique. Plasma, epithelial lining fluid (ELF), and AC pharmacokinetics were derived by noncompartmental methods. C max/90% minimum inhibitory concentration (MIC90) ratios, area under the concentration-time curve (AUC)/MIC90 ratios, intrapulmonary drug exposure ratios, and percent time above MIC90 during the dosing interval (%T > MIC90) were calculated for recently reported respiratory pathogens. The kinetics were nonlinear, i.e., not proportional to dose. In the 150-mg-dose group, the C max (mean ± standard deviations), AUC0-24, and half-life for plasma were 0.181 ± 0.084 μg/ml, 0.902 ± 0.469 μg · h/ml, and 4.85 ± 1.10 h, respectively; for ELF the values were 0.9 ± 0.2 μg/ml, 11.4 μg · h/ml, and 6.43 h, respectively; for AC the values were 12.7 ± 6.4 μg/ml, 160.8 μg · h/ml, and 10.0 h, respectively. In the 300-mg-dose group, the C max (mean ± standard deviations), AUC0-24, and half-life for plasma were 0.500 ± 0.168 μg/ml, 3.067 ± 1.205 μg · h/ml, and 4.94 ± 0.66 h, respectively; for ELF the values were 2.7 ± 2.0 μg/ml, 24.15 μg · h/ml, and 5.26 h, respectively; for AC the values were 55.4 ± 38.7 μg/ml, 636.2 μg · h/ml, and 11.6 h, respectively. We concluded that the C max/MIC90 ratios, AUC/MIC90 ratios, %T > MIC90 values, and extended plasma and intrapulmonary half-lives provide a pharmacokinetic rationale for once-daily administration and are favorable for the treatment of cethromycin-susceptible pulmonary infections.

scholarly journals Vancomycin Dosing in Healthy-Weight, Overweight, and Obese Pediatric Patients

2014 ◽  
Vol 19 (3) ◽  
pp. 182-188
Author(s):  
Lea S. Eiland ◽  
Kalyani B. Sonawane
Keyword(s):  
Serum Concentration ◽  
Pediatric Patients ◽  
Therapeutic Monitoring ◽  
Pharmacokinetic Parameters ◽  
Obese Patients ◽  
Healthy Weight ◽  
Serum Concentrations ◽  
Trough Serum Concentration ◽  
Trough Serum ◽  
Dosing Regimens

OBJECTIVES: With an increase in vancomycin resistance and the prevalence of obesity in children, alterations of vancomycin dosing regimens may be necessary to achieve target serum concentrations. The primary objective of this study was to describe initial vancomycin dosing with resulting serum concentrations in healthy-weight and overweight/obese children. Secondary objectives include comparing vancomycin dosing regimens of healthy-weight and overweight/obese patients that produced target trough serum concentrations and evaluating the likelihood of attaining target concentrations by patient characteristics. METHODS: This retrospective review evaluated healthy-weight and overweight/obese patients, aged 2 to 18 years, who had vancomycin trough serum concentrations obtained between 2005 and 2010. Vancomycin dosing, initial trough serum concentrations, pharmacokinetic parameters, and patient demographics were collected for analysis. Target trough serum concentrations were defined as 10 to 20 mg/L. RESULTS: The study included 98 patients (48 healthy weight, 50 overweight/obese) of which only 14 patients (14.2%, 6 healthy weight, 8 obese) reached a target trough serum concentration with empiric dosing. No difference was found between the mean daily dosing of vancomycin that produced target trough serum concentrations in healthy-weight or overweight/obese patients (53.63 mg/kg/day vs 51.6 mg/kg/day, respectively). Demographic or clinical characteristics were not found to be associated with the likelihood of target trough serum concentration attainment. CONCLUSIONS: Vancomycin dosing in healthy-weight and overweight/obese pediatric patients did not reach target trough serum concentrations most of the time. In obtaining initial target serum concentrations, no dosing difference was identified for overweight/obese patients compared with healthy-weight patients. Alternate dosing strategies, therapeutic monitoring, and clinical outcomes should continue to be evaluated in this population.

scholarly journals Absence of Effect of Rufloxacin on Theophylline Pharmacokinetics in Steady State

1998 ◽  
Vol 42 (9) ◽  
pp. 2359-2364 ◽  
Author(s):  
Martina Kinzig-Schippers ◽  
Uwe Fuhr ◽  
Marina Cesana ◽  
Carola Müller ◽  
A. Horst Staib ◽  
...  
Keyword(s):  
Steady State ◽  
Adverse Events ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Reversed Phase ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Elimination Phase ◽  
Once Daily ◽  
Model Independent

ABSTRACT Several quinolone antibacterial agents are known to inhibit the metabolism of theophylline, with the potential to cause adverse events due to raised theophylline concentrations during coadministration. A randomized crossover study was therefore conducted with 12 healthy male volunteers (ages, 23 to 34 years; body weight, 64 to 101 kg) to evaluate a possible interaction between rufloxacin and theophylline. Both drugs were administered at steady state. Following the administration of an oral loading dose of 400 mg on day 1, rufloxacin was given orally at 200 mg once daily on days 2 to 7 during one period only. During both periods, 146 mg of theophylline was administered orally twice daily for 3 days (which were days 4 to 6 of the rufloxacin coadministration period) and intravenously once the next morning to test for an interaction. Theophylline and rufloxacin concentrations were measured by reversed-phase high-pressure liquid chromatography, the pharmacokinetics of theophylline at steady state following administration of the last dose were calculated by compartment-model-independent methods. To compare the treatments, analysis of variance-based point estimates and 90% confidence intervals (given in parentheses) were calculated for the mean ratios of the pharmacokinetic parameters from the test (rufloxacin coadministration) over those from the reference (theophylline without rufloxacin) period. These were as follows: maximum concentration at steady state, 1.01 (0.96 to 1.07); area under the concentration-time curve from 0 to 12 h, 0.98 (0.94 to 1.02); half-life, 0.99 (0.95 to 1.03); total clearance at steady state, 1.02 (0.99 to 1.06); and volume of distribution in the elimination phase, 1.01 (0.97 to 1.05). In conclusion, rufloxacin did not affect theophylline pharmacokinetics at steady state. Therefore, therapeutic coadministration of rufloxacin and theophylline is not expected to cause an increased incidence of theophylline-related adverse events.

scholarly journals Levofloxacin Pharmacokinetics and Pharmacodynamics in Patients with Severe Burn Injury

2006 ◽  
Vol 50 (6) ◽  
pp. 1937-1945 ◽  
Author(s):  
Tyree H. Kiser ◽  
Dorie W. Hoody ◽  
Marilee D. Obritsch ◽  
Colleen O. Wegzyn ◽  
Paulus C. Bauling ◽  
...  
Keyword(s):  
Burn Injury ◽  
Treatment Strategies ◽  
Pharmacokinetic Parameters ◽  
Severe Burn ◽  
Time Curve ◽  
Once Daily ◽  
Gram Negative ◽  
Severe Burn Injuries ◽  
Gram Negative Organisms ◽  
Systemic Infections

ABSTRACT Levofloxacin pharmacokinetics were studied in 11 patients with severe burn injuries. Patients (values are means ± standard deviations; age, 41 ± 17 years; weight, 81 ± 12 kg; creatinine clearance, 114 ± 40 ml/min) received intravenous levofloxacin at 750 mg (n = 10 patients) or 500 mg (n = one patient) once daily. Blood samples were collected on day 1 of levofloxacin therapy; eight patients were studied again on days 4 to 6. The pharmacodynamic probability of target attainment (PTA) was evaluated by Monte Carlo simulation. Mean systemic clearance, half-life, and area under the concentration-time curve over 24 h after levofloxacin at 750 mg were 9.0 ± 3.2 liters/h, 7.8 ± 1.6 h, and 93 ± 31 mg · h/liter, respectively. There were no differences in pharmacokinetic parameters between day 1 and day 4; however, large intrapatient and interpatient variability was observed. Levofloxacin pharmacokinetics in burned patients were similar to those reported in other critically ill populations. Levofloxacin at 750 mg achieved >90% PTA for gram-negative and gram-positive pathogens with MICs of ≤0.5 μg/ml and MICs of ≤1 μg/ml, respectively. However, satisfactory PTA was not obtained with less-susceptible gram-negative organisms with MICs of 1 μg/ml or any organism with a MIC of ≥2 μg/ml. The results of this study indicate that levofloxacin should be administered at 750 mg/day for treatment of systemic infections in severely burned patients. However, even 750 mg/day may be inadequate for gram-negative organisms with MICs of 1 to 2 μg/ml even though they are defined as susceptible. Alternative antibiotics or treatment strategies should be considered for infections due to these pathogens.

Vancomycin Pharmacokinetics in Neonates and Infants: A Retrospective Evaluation

1993 ◽  
Vol 27 (4) ◽  
pp. 490-496 ◽  
Author(s):  
Michael D. Reed ◽  
William H. Asbury ◽  
Edress H. Darsey ◽  
W. Brian Rose ◽  
John E. Murphy ◽  
...  
Keyword(s):  
Body Weight ◽  
Steady State ◽  
Pharmacokinetic Parameters ◽  
Serum Concentrations ◽  
Vancomycin Dosage ◽  
Trough Concentrations ◽  
The Mean ◽  
Group 2 ◽  
Current Loading ◽  
Group 1

OBJECTIVE: To evaluate the frequency with which current loading and maintenance vancomycin dosages achieve target serum concentrations based on pharmacokinetic parameters obtained after the initial dose. Also, to identify the daily vancomycin dosage necessary to achieve target serum concentrations at steady-state and to determine if any relationships exist between vancomycin pharmacokinetic parameters and various patient characteristics. SETTING: Neonatal intensive care unit (NICU) at Georgia Baptist Medical Center. PATIENTS/METHODS: Twenty-three infants with suspected or documented gram-positive infection who received intravenous vancomycin between July 1990 and November 1991 were included in this retrospective analysis. Gestational age ranged from 23 to 41 weeks and postconceptional age (PCA) at the time of the study ranged from 26 to 46 weeks. Vancomycin therapy was initiated with a loading dose of 15 mg/kg, followed by a maintenance dosage of 20–30 mg/kg/d, which was usually given as 10 mg/kg q8–12h. All vancomycin doses were administered using a syringe pump. Peak and trough serum concentrations were obtained following the first dose. Vancomycin pharmacokinetic parameters were determined using a one-compartment model. Infants receiving indomethacin within two weeks prior to study were analyzed separately (group 2, n=4). All other infants were included in group 1 (n=19). RESULTS: For group 1, vancomycin clearance (CI), volume of distribution (Vd), and half-life were (mean ± 1 SD) 0.072 ± 0.032 L/kg/h, 0.52 ± 0.08 L/kg, and 5.6 ± 1.6 hours, respectively. For both groups, loading doses provided 1-hour postinfusion peak concentrations of 25–35 mg/L in one of every two infants studied, whereas only three percent of initial maintenance doses were projected to provide desired peak and trough concentrations at steady-state. For group 1, the mean daily dosage necessary to provide target peak (25–35 mg/L) and trough (5–10 mg/L) concentrations at steady-state was larger than that initially prescribed (29.6 ± 13.1 vs. 22.2 ± 4.7 mg/kg/d). For group 2, the mean daily dosage required to achieve target peak and trough concentrations at steady-state was smaller than that initially prescribed (14.8 ± 4.3 vs. 20.0 ±0.1 mg/kg/d) and was exactly half of that required for group 1. Excellent correlations were observed between PCA and vancomycin Cl (L/h) (r=0.92; p<0.0001), body weight and Vd (L) (r=0.94; p<0.0001), body weight and vancomycin Cl (L/h) (r=0.85; p<0.0001), PCA and Vd (L) (r=0.89; p<0.0001), and body surface area and Vd (L) (r=0.93; p<0.0001) for group 1. Moderate correlations were also noted between PCA and Cl relative to body weight (L/kg/h), postnatal age and Cl (L/kg/h), and PCA and vancomycin dosage requirements (mg/kg/d). No linear correlation was observed between any patient characteristic and Vd standardized for body weight. CONCLUSIONS: Our data demonstrate the need for a more accurate method of estimating initial vancomycin dosage requirements in this NICU population. Although some of the relationships revealed in this study could be used to determine vancomycin dosage for infants in the range of approximately 30–36 weeks PCA, we hesitate to suggest this approach presently because of the potential limitations of our study design. Further prospective study is needed to confirm these observations. In addition, further study is necessary to describe the time course of the interaction between vancomycin and indomethacin in infants with successful and unsuccessful closure of their patent ductus arteriosus.

scholarly journals Pharmacokinetics of Cefepime in Patients with Thermal Burn Injury

1999 ◽  
Vol 43 (12) ◽  
pp. 2848-2854 ◽  
Author(s):  
Charles R. Bonapace ◽  
Roger L. White ◽  
Lawrence V. Friedrich ◽  
E. Douglas Norcross ◽  
John A. Bosso
Keyword(s):  
Steady State ◽  
Healthy Volunteers ◽  
Half Life ◽  
Burn Injury ◽  
Pharmacokinetic Parameters ◽  
Albumin Concentration ◽  
Burn Patients ◽  
Serum Concentrations ◽  
Thermal Burn ◽  
Dosing Regimens

ABSTRACT The pharmacokinetics of cefepime following administration of a single 2-g dose were evaluated for 12 adult patients with thermal burn injury and suspected or documented infection. Serial blood and urine samples for cefepime concentration determination were obtained for 24 h following drug administration. Serum and urine cefepime concentrations were determined by high-performance liquid chromatography and serum concentrations were fit to a two-compartment pharmacokinetic model. Mean (standard deviation [SD]) age, actual body weight (ABW), percent total body surface area burned, and days postburn at the time of study were 41 (13) years, 84 (22) kg, 36 (17)%, and 9 (3) days, respectively. Mean (SD) measured creatinine clearance (CLCR), total clearance (CLT), renal clearance (CLR), alpha phase half-life, beta phase half-life, and volume of distribution at steady state (V SS) were 135 (31) ml/min, 8.8 (2.4) liters/h, 8.1 (2.0) liters/h, 0.33 (0.14) h, 2.8 (0.6) h, and 0.43 (0.10) liters/kg ABW, respectively. Cefepime CLT and CLR in burn patients were similar to previously reported values for healthy volunteers when normalized by CLCR. Stepwise multiple regression was used to associate CLT with CLCR and days postburn (r 2 = 0.861), CLRwith CLCR and days postburn (r 2 = 0.773), nonrenal clearance with percent third-degree (% 3°) burn and albumin concentration (r 2 = 0.550), andV SS only with % 3° burn (r 2 = 0.624). Simulated steady-state serum concentrations obtained by using the patients’ pharmacokinetic parameters exceeded the susceptibility interpretive standard (breakpoint) of cefepime for at least 60% of the dosing interval with dosing regimens of 1 g every 8 h (q8h), 2 g q8h, and 2 g q12h. Despite differences in pharmacokinetic parameters between our patients and healthy volunteers, it appears that these dosing regimens may be adequate in similar burn patients.

Effect of rifampicin pretreatment on the oral bioavailability of domperidone in healthy human volunteers

2015 ◽  
Vol 30 (4) ◽  
Author(s):  
Adukondalu Devandla ◽  
Shravan Kumar Yamsani ◽  
Madhusudan Rao Yamsani
Keyword(s):  
Compartmental Model ◽  
Pharmacokinetic Parameters ◽  
Serum Concentrations ◽  
Reverse Phase Hplc ◽  
Reverse Phase ◽  
Healthy Human ◽  
Once Daily ◽  
Treatment Conditions ◽  
Human Volunteers ◽  
Daily Dose

AbstractIncreased exsorption of domperidone was observed from different parts of the small intestine of the rat after pretreatment with rifampicin by the everted sac method. Based on theAfter an overnight fast, 20 mg domperidone was administered to the volunteers, either alone or after 6 days pretreatment with a once daily dose of 600 mg rifampicin. Serum concentrations of domperidone were estimated by reverse phase HPLC. Pharmacokinetic parameters were determined based on non-compartmental model analysis using the computer program kinetica.Rifampicin pretreatment decreased Cmax, AUCoThis interaction may have clinical significance when domperidone is co-administered with rifampicin in chronic treatment conditions, such as tuberculosis, leprosy and other infections of joints, bones, etc.

Cefepime Dosing in Neonates: What is the Evidence?

2019 ◽  
Author(s):  
Danielle McDonald ◽  
Pooja Shah
Keyword(s):  
Clinical Practice ◽  
English Language ◽  
Inhibitory Concentration ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Serum Concentrations ◽  
Dosing Regimen ◽  
Dosing Interval ◽  
Dosing Frequency ◽  
Dosing Strategies

Abstract Objective Recommended cefepime dosing strategies in neonates varies in commonly utilized dosing references with regard to dose and frequency. The objective of this review is to summarize and evaluate the available literature describing cefepime dosing in neonatal patients. Study Design We performed a literature review in MEDLINE using the keyword cefepime. The search was limited to the English language, humans, and patients <2 months of age. We evaluated four pharmacokinetic studies and two studies describing the use of cefepime in clinical practice. Results The available studies assessing cefepime serum concentrations in neonatal patients demonstrated maintenance of adequate pharmacokinetic parameters when utilizing a dosing frequency of every 12 hours, specifically for organisms with a minimum inhibitory concentration (MIC) ≤ 8 mg/L. In studies evaluating clinical outcomes of cefepime use in neonates, the most frequent adverse effects reported included seizures and hypophosphatemia. Microbiologic cure was demonstrated with a dosing regimen of 50 mg/kg per dose every 12 hours. Conclusion Cefepime dosed 30 to 50 mg/kg per dose every 12 hours may be appropriate to achieve a concentration two to four times above an MIC ≤ 8 mg/L for at least 60% of the dosing interval in neonatal patients.

Effectiveness of a Gentamicin Dosing Protocol Based on Postconceptional Age: Comparison to Published Neonatal Guidelines

1992 ◽  
Vol 26 (4) ◽  
pp. 534-538 ◽  
Author(s):  
Michael D. Reed ◽  
Ana M. Lopez-Samblas ◽  
Carmen L. Torres ◽  
Helena Wang ◽  
William J. Feuer ◽  
...  
Keyword(s):  
Medical Center ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Data ◽  
Serum Concentrations ◽  
Group I ◽  
Trough Serum ◽  
Significant Difference ◽  
Postconceptional Age ◽  
Trough Concentrations ◽  
Group Ii

OBJECTIVE: To evaluate the effectiveness of a gentamicin dosing protocol based on postconceptional age in producing therapeutic serum concentrations and to compare the protocol with commonly used gentamicin dosing guidelines. DESIGN: During the initial three months of this study infants were dosed according to physician discretion (group I). In the subsequent three-month period patients were dosed according to a postconceptional age dosing schedule (group II). SETTING: Infants were enrolled after being admitted to the Newborn Intensive Care Unit at the University of Miami/Jackson Memorial Medical Center. PATIENTS: Infants less than 37 weeks gestational age with normal renal function, not receiving indomethacin, and requiring gentamicin treatment were enrolled. Fifty-nine infants were enrolled into group I (median weight 1300 g [range 720–3300]), postconceptional age 29 weeks [26–37]); and 68 infants were enrolled into group II (weight 970 g [530–3000], postconceptional age 29 weeks [24–36]). INTERVENTION: Patients in group II were dosed according to the following protocol: postconceptional age <30 weeks, 3.0 mg/kg q24h, and postconceptional age 30–37 weeks, 2.5 mg/kg q18h. Peak and trough serum gentamicin concentrations were obtained in all study patients. Pharmacokinetic parameters were calculated from measured serum concentrations. Using the calculated pharmacokinetic data, peak and trough serum concentrations were simulated for five published neonatal dosing guidelines and the proposed postconceptional age protocol. MAIN OUTCOME MEASURES: The number of therapeutic serum gentamicin concentrations resulting from the dosing guidelines studied were compared. RESULTS: Measured trough concentrations differed significantly between the two groups with 35 percent of patients in group I and 90 percent of patients in group II having trough values <2 mg/L (p<0.001). There was no significant difference in measured peak concentrations between groups. Simulated trough concentrations were significantly different when postconceptional age dosing was compared with commonly used protocols (p<0.0001) with the highest percentage of concentrations <2 mg/L (89 percent) resulting from the proposed postconceptional age guidelines. CONCLUSIONS: These data suggest that the proposed postconceptional age protocol is reproducible and reliable in achieving therapeutic gentamicin serum concentrations in neonates.

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