Phenobarbital Pharmacokinetics in Infants Using Saliva as a Biologic Fluid

1994 ◽  
Vol 10 (6) ◽  
pp. 250-254
Author(s):  
Stella Gutierrez ◽  
Marta Vázquez ◽  
Amanda Amodio ◽  
Gustavo Giachetto ◽  
Diana Moller ◽  
...  
Keyword(s):  
Medical Center ◽  
Randomized Study ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Loading Dose ◽  
Seizure Disorders ◽  
Elimination Half ◽  
Significant Difference ◽  
Daily Dose ◽  
Trough Concentrations

Objective: To determine the pharmacokinetic parameters of phenobarbital in infants, using saliva as a biologic fluid, and to correlate the parameters obtained from saliva data with those obtained from plasma data. Design: A prospective, randomized study. Setting: Hospitalized patients at the Medical Center Pereira Rossell, a pediatric hospital in Montevideo, Uruguay. Patients: Sixteen infants with seizure disorders were included in the study. None of them was treated with other medications. Interventions: A direct intravenous loading dose of phenobarbital 10 mg/kg was administered, followed by a maintenance dosage of 5 mg/kg/d (once- or twice-daily dosing) given 12 hours after the loading dose. Main Outcome Measures: Saliva and plasma samples were obtained 6 and 12 hours after the loading dose and 3 days after the initiation of the maintenance dose (trough sample): the samples were analyzed by HPLC and the elimination half-life (t1/2), the volume of distribution (Vd), and the percentage of unbound drug in plasma (UDP) were calculated. Results: The t1/2 obtained from plasma and saliva data was 30 hours; the Vd was 0.73 L/kg from plasma data and 2.4 L/kg from saliva data; and the UDP was 75 percent. Trough concentrations showed no significant difference between treatments. Conclusions: Saliva is a useful biologic fluid to determine phenobarbital pharmacokinetic parameters, mainly in pediatric patients. Moreover, a single daily dose of phenobarbital is sufficient to obtain therapeutic concentrations.

Gentamicin Pharmacokinetics in Elderly Patients with Normal Renal Function

1994 ◽  
Vol 10 (1) ◽  
pp. 14-17 ◽  
Author(s):  
Ji M. Koo ◽  
Donald R. Miller ◽  
Charles D. Peterson
Keyword(s):  
Renal Function ◽  
Elderly Patients ◽  
Normal Renal Function ◽  
Medical Center ◽  
Elimination Rate ◽  
The Elderly ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Trough Concentrations ◽  
The Mean

Objective: To establish the pharmacokinetic parameters of gentamicin in elderly patients and to compare predicted concentrations based on the Dettli method, with actual concentrations. Design: Measurement of gentamicin concentrations and pharmacokinetic parameters in a consecutive patient sample with comparison to ones predicted by the Dettli method. Setting: Medical and surgical units in a Veterans Affairs Medical Center. Patients: Forty-six consecutive elderly men treated with gentamicin for documented or presumed infection and had stable, normal renal function. Main Outcome Measures: The following information was calculated or measured: elimination rate constant (kel), elimination half-life, volume of distribution (Vd), and peak and trough concentrations. Results: The mean kel (0.16 ± 0.05 h−1) was not significantly different (p=0.2) from the Dettli method prediction, and the mean Vd (0.36 ± 0.1 L/kg) was 37 percent higher than that usually reported. Actual peak and trough concentrations were significantly lower (both p<0.01) than predicted concentrations. Conclusions: Based on our findings, higher than recommended loading doses and longer dosage intervals may be required in the elderly. The Dettli method is useful to estimate kel in the elderly.

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.

Influence of cyp2d6 polymorphisms on pharmacokinetics, efficacy and safety of antipsychotics

2018 ◽  
pp. 26-39
Author(s):  
А.А. Курылев ◽  
Б.В. Андреев
Keyword(s):  
Genetic Polymorphisms ◽  
Atypical Antipsychotics ◽  
Retrospective Studies ◽  
Pharmacokinetic Parameters ◽  
Clinical Routine ◽  
Elimination Half ◽  
Daily Dose ◽  
Comparison Groups ◽  
Cyp2d6 Polymorphisms ◽  
Positive Significant Correlation

Несмотря на доступность в клинической практике широкого круга классических и атипичных антипсихотиков (АП), по-прежнему наблюдается широкая вариабельность ответа на психофармакотерапию. Эта вариабельность обусловлена генетической гетерогенностью как самой шизофрении, так и метаболизма АП. Стандартные назначаемые дозы АП далеко не всегда являются оптимальными. Генетическая вариабельность систем биотрансформации и биодоступности АП могут играть значимую роль в формировании ответа на терапию и развитии нежелательных реакций. Целью исследования стало проведение обзора литературы по проблеме клинической эффективности применения генотипирования полиморфизмов CYP2D6 при терапии антипсихотиками. Большинство фармакокинетических исследований обнаруживают сильную достоверную положительную корреляцию метаболического статуса CYP2D6, определенного путем генотипирования полиморфизмов CYP2D6 и фармакокинетических параметров АП (AUC, период полувыведения, клиренс). Однако статистически достоверных связей между полиморфизмами CYP2D6 и эффективностью терапии АП в большинстве исследований обнаружено не было, прежде всего из-за недостаточного количества участников, гетерогенности сравниваемых когорт, применении различных АП и использовании разных критериев эффективности. Перспективные исследования с хорошо сбалансированными группами сравнения, а также масштабные ретроспективные исследования демонстрируют достоверную корреляцию метаболического статуса CYP2D6 и частоты развития нежелательных реакций АП (лекарственный паркинсонизм и поздняя дискинезия). Для более точной оценки величины вклада генетических полиморфизмов CYP2D6 в эффективность и безопасность психофармакотерапии необходимы масштабные перспективные клинические исследования. Although a number of typical and atypical antipsychotics (AP) have been discovered and used in psychiatric clinical practice the variability in response to AP is quite high. This variability is partially explained by a genetic heterogeneity of schizophrenia and metabolism of AP. The standard prescribed antipsychotic daily dose is not always optimal. Genetic variability of biotransformation and bioavailability of AP may significantly influence on therapeutic effect and tolerability. The aim of the study was to perform literature review of studies evaluating the correlation of CYP2D6 genetic polymorphisms and AP pharmacokinetics, effectiveness and safety. Most pharmacokinetics studies show high positive significant correlation between CYP2D6 metabolic activity, determined by CYP2D6 polymorphisms genotyping and AP pharmacokinetic parameters (AUC, elimination half-life, clearance etc.). However the majority of studies were failed to demonstrate significant correlation between CYP2D6 polymorphisms and AP effectiveness mainly due to inadequate number of patient, heterogeneous cohorts, different AP and effectiveness criteria used. Prospective studies with balanced comparison groups and large retrospective studies showed significant correlation between CYP2D6 metabolic status and the frequency of AP induced AEs (parkinsonism and tardive dyskinesia). To better assess the influence of CYP2D6 genetic polymorphisms on AP effectiveness and safety in clinical routine large prospective well designed clinical studies are needed.

scholarly journals Pharmacokinetics of Intravenous Piperacillin Administration in Patients Undergoing On-Line Hemodiafiltration

2009 ◽  
Vol 53 (8) ◽  
pp. 3266-3268 ◽  
Author(s):  
Kook-Hwan Oh ◽  
Chiweon Kim ◽  
Hankyu Lee ◽  
Hajeong Lee ◽  
Ji Yong Jung ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Total Body Clearance ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Recovery Method ◽  
Elimination Half ◽  
On Line ◽  
The Mean ◽  
Total Body ◽  
Body Clearance

ABSTRACT The pharmacokinetic characteristics of piperacillin sodium were studied in five volunteers undergoing on-line hemodiafiltration (HDF). The subjects were given 2 g of piperacillin sodium intravenously over 1 min and placed on on-line HDF for 4 h starting at 60 min after the piperacillin infusion. Noncompartmental models were employed for estimation of the pharmacokinetic parameters, and intradialytic piperacillin clearance was calculated by the recovery method. The mean volume of distribution and the elimination half-life were 0.27 ± 0.13 liter/kg (mean ± standard deviation) and 1.1 ± 0.6 h, respectively. The total body clearance of piperacillin was 0.19 ± 0.08 liter/h/kg. Piperacillin clearance through on-line HDF was 0.11 ± 0.06 liter/h/kg. The mean serum piperacillin concentration was 4.0 ± 1.9 μg/ml at the end of the 4-h on-line HDF session. The concentration of infused piperacillin recovered in the dialysate was 527 ± 236 mg (26.3% ± 11.8%). We suggest the replacement of 500 mg of piperacillin after each on-line HDF session.

scholarly journals Safety, toleration, and pharmacokinetics of intravenous azithromycin.

1996 ◽  
Vol 40 (11) ◽  
pp. 2577-2581 ◽  
Author(s):  
D R Luke ◽  
G Foulds ◽  
S F Cohen ◽  
B Levy
Keyword(s):  
Half Life ◽  
Active Drug ◽  
Slow Release ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Concentration Time ◽  
Elimination Half ◽  
The Mean ◽  
Male Subjects

To date, the clinical pharmacology of large intravenous doses of azithromycin has not been described. In the present study, single 2-h intravenous infusions of 1, 2, and 4 g of azithromycin were administered to three parallel groups (in each group, six received active drug and two received placebo) of healthy male subjects. Toleration (assessed by scores of subject-administered visual analog scale tests spanning 0 [good] to 10 [poor]), safety, pharmacokinetics, and serum motilin levels were monitored for up to 240 h after the start of each intravenous infusion. Mean nausea scores of 0.0, 0.0, 1.0, and 0.5 and abdominal cramping scores of 0.0, 0.0, 0.4, and 0.4 for 12-h periods after doses of 0, 1, 2, and 4 g of azithromycin, respectively, suggested that azithromycin was well tolerated. Because of the standardized 1-mg/ml infusates, all subjects in the 4-g dosing group complained of an urgent need to urinate. There were no consistent trends in endogenous motilin levels throughout the study. The maximum concentration of azithromycin in serum (10 micrograms/ml after a 4-g dose) and the area under the concentration-time curve (82 micrograms.h/ml after a 4-g dose) were dose related. The mean pharmacokinetic parameters were an elimination half-life of 69 h, total systemic clearance of 10 ml/min/kg, and a volume of distribution at steady state of 33.3 liters/kg. The pharmacokinetic results suggest that the long half-life of azithromycin is due to extensive uptake and slow release of the drug from tissues rather than an inability to clear the drug. Single intravenous doses of up to 4 g of azithromycin in healthy subjects are generally well tolerated, and quantifiable concentrations may persist in serum for 10 days or more.

scholarly journals 1575. Vancomycin Loading Doses and Nephrotoxicity on Medicine Teaching Services

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S575-S575
Author(s):  
Phillip Wagner ◽  
Jon Arnold ◽  
Kathleen R Sheridan
Keyword(s):  
Drug Exposure ◽  
Standard Dose ◽  
Medical Center ◽  
Academic Medical Center ◽  
Kidney Injury ◽  
Loading Dose ◽  
Academic Medical ◽  
Trough Concentrations ◽  
Seriously Ill Patients ◽  
The Relationship

Abstract Background IDSA guidelines recommend the usage of a loading dose when using vancomycin for seriously ill patients to rapidly achieve adequate trough concentrations. While the relationship between vancomycin and nephrotoxicity is the focus of many studies, and with the strength of that relationship still debated, few studies have examined the relationship between vancomycin loading doses and nephrotoxicity. Methods We performed a retrospective cohort study examining vancomycin dosing for internal medicine teaching services’ patients over the 2014–15 academic year at one academic medical center. We generated a list of all hospitalized patients aged 18–85 who received vancomycin and were admitted to a teaching service. Patient data were extracted from the inpatient EMR via manual chart review. Patients were excluded if their pretreatment calculated glomerular filtration rate (GFR) was less than 50 mL/minute, if they received less than three doses of vancomycin, or if their initial dose was subtherapeutic (<10 mg/kg). Nephrotoxicity was determined by 7-day acute kidney injury (AKI) rate. Patients in the loading dose (>20 mg/kg) cohort were compared with those in the standard dose cohort (10–20 mg/kg). Our primary modeling used multi-variable logistic regression with AKI as our outcome of interest. Results 438 of the initial 804 patients were enrolled. The loading dose (n = 365, 83%) and standard dosing (n = 73, 17%) cohorts were not significantly different regarding demographics, GFR, nephrotoxic drug exposure, total vancomycin received, trough levels, or comorbidities, and were only significantly different regarding body mass index (BMI). The 7-day AKI rate was not significantly different between the two arms (6.3% in the standard dosing arm and 8.2% in the loading dose arm P = 0.6). AKI rate significantly increased in both arms in the setting of concurrent piperacillin–tazobactam and vancomycin administration (OR 2.5, P = .04). There was no association between BMI and AKI. Conclusion Few studies have examined the relationship between nephrotoxicity and vancomycin loading doses. The results of this study provide evidence that the use of loading doses is not significantly associated with increased 7-day AKI rate. Disclosures All authors: No reported disclosures.

Pharmacokinetic Evaluation of anti-HIV Drug Interactions: Effect of Zidovudine on 2′-3′-Dideoxyinosine Kinetics in Monkeys

1993 ◽  
Vol 4 (3) ◽  
pp. 155-159 ◽  
Author(s):  
M. Qian ◽  
A. R. Swagler ◽  
M. Mehta ◽  
C.T. Vishwanathan ◽  
J. M. Gallo
Keyword(s):  
Dose Group ◽  
Plasma Concentrations ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
High Dose ◽  
Combination Regimen ◽  
Time Profiles ◽  
Elimination Half ◽  
Constant Rate ◽  
Rate Infusion

The current investigation was conducted to determine if zidovudine (AZT) altered the pharmacokinetics of dideoxyinosine (ddl) in non-hurnan primates, an appropriate animal model for AZT and ddl pharmacokinetics in human. Each of nine animals received 20 mg kg−1 of ddl intravenously in the absence and presence of two different dosage regimens of AZT. For each combination regimen, AZT was administered as a combined i.v. bolus-constant rate infusion regimen for 30 min that produced AZT plasma concentrations of about 4 μg ml−1 in six animals (low dose group) and 11 μg ml−1 in three others (high dose group). Serial blood samples were collected, and pharmacokinetic parameters for ddl were calculated based on plasma ddl concentrations measured by HPLC techniques. The pharmacokinetics of ddl given alone in the first phase of the low ( n = 6) and high ( n = 6) dose AZT groups, resulted in a mean elimination half-life 1.54 and 1.9h, a mean total clearance of 0.62 and 0.731 h−1 kg−1, and a mean steady state volume of distribution of 1.02 and 0.891 kg−1, respectively. Following combined ddl and AZT administrations, in both the low and high dose AZT groups, plasma concentration-time profiles of ddl were similar for each monkey, and no statistical differences were observed in the pharmacokinetic parameters compared to those obtained when ddl was given alone. The fact that AZT does not alter the pharmacokinetics of ddl at the range of AZT dose studied provides a basis for rational dosage design for combined ddl and AZT treatments in HIV infection.

Phamacokinetics (PK) Substudy of Rituximab in a Prospective Clinical Trial for Pediatric Chronic Immune Thrombocytopenic Purpura (cITP).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1243-1243 ◽  
Author(s):  
Carolyn M. Bennett ◽  
James B. Bussel ◽  
Brigitta U. Mueller ◽  
Thomas C. Abshire ◽  
Hadi Sawaf ◽  
...  
Keyword(s):  
Analysis Of Variance ◽  
Pediatric Patients ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Half Time ◽  
Age Cohorts ◽  
Elimination Half ◽  
Significant Difference ◽  
Older Subjects ◽  
The Difference

Abstract Rationale: Rituximab dosing in pediatric patients is derived from body surface area-based “standard” adult lymphoma regimens. PK data for rituximab in children are lacking. Methods: We evaluated serum rituximab levels in a subset of 36 children and adolescents with severe cITP treated on a prospective phase I/II study. Patients received four weekly infusions, 375mg/m2/dose. Trough and 30-minute, 24- and 48-hour (hr) post-infusion levels were obtained with doses 1 and 4, and 7 days after dose 1. PK parameters were obtained separately for each patient at the 1-wk and 4-wk infusions by fitting a two-compartment model. Two-factor analysis of variance was employed to compare parameters between younger (2–9 years) and older (10–18 years) subjects and between responders and non-responders at the two infusion times. Results: Fourteen patients had PK measurements at week 1 and eleven at week 4 (Table). The median initial volume of distribution (V1), for all patients, calculated by back-extrapolation to t0, approximated plasma volume, 53 mL/kg. Kinetics fit a two-component model, with relatively rapid initial half-time (exit) reflecting distribution out of plasma space, and equilibration representing slow return into the vascular pool. The drug elimination half-time was too slow to observe in these 7-day periods. Apparent half-time for initial redistribution from the plasma space was significantly longer for younger subjects at week 4 than at week 1 and than for older subjects at week 4 (Table). By comparison, in studies of 14 adults with lymphoma treated with rituximab at the same dosage regimen, the manufacturer reports mean serum half-time of 76 hrs (range, 31–153) at week 1 and 205 hrs (range, 84 – 407) at week 4. In this PK sub-study, we found no significant difference in kinetic parameters between the 5 responders (defined by sustained platelet count &gt;50,000/mm3 at week 12) and 11 non-responders. Conclusion: In this small number of pediatric patients with cITP treated with 4 weekly infusions of rituximab, the half-time was longer for younger subjects at week 4 than week 1 and than for older subjects at week 4. Trough levels at week 4 do not represent steady state because the elimination half-time is long. The reason for the difference between the two age cohorts is not readily apparent, but we propose that the shorter exit half-time in younger patients at week 1 compared to week 4 corresponds to a higher number of initially accessible CD20 binding sites (B cells) in young children. PK parameters of rituximab distribution at weeks 1 and 4 Age (yr) Week 1 n Week4 n Median (min, max) Median (min, max) *Age x week interaction significant in two-way analysis of variance, p&lt;0.015 V1 (mL/kg) All 53 (35–76) 14 54 (35–74) 11 2–9 54 (43–76) 7 62 (54–74) 4 10–18 52 (35–73) 7 49 (35–62) 7 Exit Half-time (hr) All 49 (16–83) 14 83 (25–193) 11 2–9 45 (31–55) 7 100 (83–193)* 4 10–18 57 (16–83) 7 57 (25–97) 7

scholarly journals Predictors of Voriconazole Trough Concentrations in Patients with Child–Pugh Class C Cirrhosis: A Prospective Study

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1130
Author(s):  
Yichang Zhao ◽  
Jingjing Hou ◽  
Yiwen Xiao ◽  
Feng Wang ◽  
Bikui Zhang ◽  
...  
Keyword(s):  
Trough Concentration ◽  
Multiple Linear Regression Model ◽  
Therapeutic Drug ◽  
Time Activity ◽  
Bivariate Correlation ◽  
Significant Difference ◽  
Daily Dose ◽  
Pugh Class ◽  
Trough Concentrations ◽  
Class C

This prospective observational study aimed to clinically describe voriconazole administrations and trough concentrations in patients with Child–Pugh class C and to investigate the variability of trough concentration. A total of 144 voriconazole trough concentrations from 43 Child–Pugh class C patients were analyzed. The majority of patients (62.8%) received adjustments. The repeated measured trough concentration was higher than the first and final ones generally (median, 4.33 vs. 2.99, 3.90 mg/L). Eight patients with ideal initial concentrations later got supratherapeutic with no adjusted daily dose, implying accumulation. There was a significant difference in concentrations among the six groups by daily dose (p = 0.006). The bivariate correlation analysis showed that sex, CYP2C19 genotyping, daily dose, prothrombin time activity, international normalized ratio, platelet, and Model for end-stage liver disease score were significant factors for concentration. Subsequently, the first four factors mentioned above entered into a stepwise multiple linear regression model (variance inflation factor <5), implying that CYP2C19 testing makes sense for precision medicine of Child–Pugh class C cirrhosis patients. The equation fits well and explains the 34.8% variety of concentrations (R2 = 0.348). In conclusion, it needs more cautious administration clinically due to no recommendation for Child–Pugh class C patients in the medication label. The adjustment of the administration regimen should be mainly based on the results of repeated therapeutic drug monitoring.

Reevaluation of Gentamicin Dosing in the Neonatal Population

1995 ◽  
Vol 11 (3) ◽  
pp. 105-109
Author(s):  
Thomas M Gray
Keyword(s):  
Rate Constant ◽  
Gestational Age ◽  
Trough Concentration ◽  
Elimination Rate ◽  
Retrospective Chart Review ◽  
Volume Of Distribution ◽  
Full Term ◽  
Pharmacokinetic Parameters ◽  
Trough Concentrations ◽  
Neonatal Population

Objective: To determine whether current recommendations for gentamicin dosing in full-term newborns yield a serum peak concentration of 6–7 μg/mL and a trough concentration less than 2 μg/mL in treating suspected neonatal sepsis. Design: Two-year retrospective chart review. Setting: Community hospital. Results: Sample consisted of 175 newborns with a gestational age ranging from 36 to 43 weeks and 188 sets of concentrations. Pharmacokinetic parameters were calculated using a one-compartment, first-order elimination model and were reported as follows: volume of distribution 0.59 kg/L, elimination rate constant (ke) 0.11 h−1 (half-life [t1/2] 6.8 h) at 36–37 weeks of age, with a significant change (p < 0.05) in rate constant occurring at 38–43 weeks of life, and ke 0.12 h−1 (t1/2 6.0 h) when using a two-tailed, two-sample t-test. Extrapolated mean peak concentrations were 5.8 ± 1.2 μg/mL and trough concentrations were 1.5 ± 0.5 μg/mL. Furthermore, 14% of newborns had an extrapolated trough concentration of 2.0 μg/mL or more. Conclusions: The current 2.5-mg/kg dosage is appropriate for the neonatal population studied. However, to decrease the number of potentially toxic trough concentrations, the initial dosing interval should be extended to every 18 hours for full-term neonates (>37 weeks gestation) with normal kidney function and for neonates with a gestational age of 36–37 weeks.

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