scholarly journals Extended-Interval Gentamicin Dosing in Achieving Therapeutic Concentrations in Malaysian Neonates

2015 ◽  
Vol 20 (2) ◽  
pp. 119-127
Author(s):  
Yee Shan Low ◽  
Sin Li Tan ◽  
Angeline SL Wan
Keyword(s):  
Body Weight ◽  
Gestational Age ◽  
Trough Concentration ◽  
Elimination Rate ◽  
Dose Interval ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Creatinine Concentration ◽  
Cross Sectional ◽  
Significant Difference

OBJECTIVE: To evaluate the usefulness of extended-interval gentamicin dosing practiced in neonatal intensive care unit (NICU) and special care nursery (SCN) of a Malaysian hospital. METHODS: Cross-sectional observational study with pharmacokinetic analysis of all patients aged ≤28 days who received gentamicin treatment in NICU/SCN. Subjects received dosing according to a regimen modified from an Australian-based pediatric guideline. During a study period of 3 months, subjects were evaluated for gestational age, body weight, serum creatinine concentration, gentamicin dose/interval, serum peak and trough concentrations, and pharmacokinetic parameters. Descriptive percentages were used to determine the overall dosing accuracy, while analysis of variance (ANOVA) was conducted to compare the accuracy rates among different gestational ages. Pharmacokinetic profile among different gestational age and body weight groups were compared by using ANOVA. RESULTS: Of the 113 subjects included, 82.3% (n = 93) achieved therapeutic concentrations at the first drug-monitoring assessment. There was no significant difference found between the percentage of term neonates who achieved therapeutic concentrations and the premature group (87.1% vs. 74.4%), p = 0.085. A total of 112 subjects (99.1%) achieved desired therapeutic trough concentration of <2 mg/L. Mean gentamicin peak concentration was 8.52 mg/L (95% confidence interval [Cl], 8.13–8.90 mg/L) and trough concentration was 0.54 mg/L (95% CI, 0.48–0.60 mg/L). Mean volume of distribution, half-life, and elimination rate were 0.65 L/kg (95% CI, 0.62–0.68 L/kg), 6.96 hours (95% CI, 6.52–7.40 hours), and 0.11 hour−1 (95% CI, 0.10–0.11 hour−1), respectively. CONCLUSION: The larger percentage of subjects attaining therapeutic range with extended-interval gentamicin dosing suggests that this regimen is appropriate and can be safely used among Malaysian neonates.

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.

scholarly journals Pharmacokinetics of intramuscularly administered aminosidine in healthy subjects.

1997 ◽  
Vol 41 (5) ◽  
pp. 982-986 ◽  
Author(s):  
T P Kanyok ◽  
A D Killian ◽  
K A Rodvold ◽  
L H Danziger
Keyword(s):  
Healthy Subjects ◽  
Randomized Clinical Trials ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
Multiple Drug ◽  
Time Data ◽  
Time Curve ◽  
First Order ◽  
Significant Difference

Aminosidine is an older, broad-spectrum aminoglycoside antibiotic that has been shown to be effective in in vitro and animal models against multiple-drug-resistant tuberculosis and the Mycobacterium avium complex. The objective of this randomized, parallel trial was to characterize the single-dose pharmacokinetics of aminosidine sulfate in healthy subjects (eight males, eight females). Sixteen adults (mean [+/- standard deviation] age, 27.6 +/- 5.6 years) were randomly allocated to receive a single, intramuscular aminosidine sulfate injection at a dose of 12 or 15 mg/kg of body weight. Serial plasma and urine samples were collected over a 24-h period and used to determine aminosidine concentrations by high-performance liquid chromatographic assay. A one-compartment model with first-order input, first-order output, and a lag time (Tlag) and with a weighting factor of 1/y2 best described the data. Compartmental and noncompartmental pharmacokinetic parameters were estimated with the microcomputer program WinNonlin. One subject was not included (15-mg/kg group) because of the lack of sampling time data. On average, subjects attained peak concentrations of 22.4 +/- 3.2 microg/ml at 1.34 +/- 0.45 h. All subjects had plasma aminosidine concentrations below 2 microg/ml at 12 h, and all but two subjects (one in each dosing group) had undetectable plasma aminosidine concentrations at 24 h. The dose-adjusted area under the concentration-time curve from 0 h to infinity of aminosidine was identical for the 12- and 15-mg/kg groups (9.29 +/- 1.5 versus 9.29 +/- 2.2 microg x h/ml per mg/kg; P = 0.998). Similarly, no significant differences (P > 0.05) were observed between dosing groups for peak aminosidine concentration in plasma, time to peak aminosidine concentration in plasma, Tlag, apparent clearance, renal clearance, elimination rate constant, and elimination half-life. A significant difference was observed for the volume of distribution (0.35 versus 0.41 liters/kg; P = 0.037) between the 12 and 15 mg/kg dosing groups. Now that comparable pharmacokinetic profiles between dosing groups have been demonstrated, therapeutic equivalency testing via in vitro pharmacokinetic and pharmacodynamic modelling and randomized clinical trials in humans should be conducted.

Vancomycin volume of distribution estimation in adults with class III obesity

2019 ◽  
Author(s):  
Ryan D Dunn ◽  
Ryan L Crass ◽  
Joseph Hong ◽  
Manjunath P Pai ◽  
Lynne C Krop
Keyword(s):  
Body Weight ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Patient Specific ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Parameter Estimates ◽  
Class Iii ◽  
Class Iii Obesity ◽  
Total Body

Abstract Purpose To compare methods of estimating vancomycin volume of distribution (V) in adults with class III obesity. Methods A retrospective, multicenter pharmacokinetic analysis of adults treated with vancomycin and monitored through measurement of peak and trough concentrations was performed. Individual pharmacokinetic parameter estimates were obtained via maximum a posteriori Bayesian analysis. The relationship between V and body weight was assessed using linear regression. Mean bias and root-mean-square error (RMSE) were calculated to assess the precision of multiple methods of estimating V. Results Of 241 patients included in the study sample, 159 (66.0%) had a BMI of 40.0–49.9 kg/m2, and 82 (34.0%) had a BMI of ≥50.0 kg/m2. The median (5th, 95th percentile) weight of patients was 136 (103, 204) kg, and baseline characteristics were similar between BMI groups. The mean ± S.D. V was lower in patients with a BMI of 40.0–49.9 kg/m2 than in those with a BMI of ≥50.0 kg/m2 (72.4 ± 19.6 L versus 79.3 ± 20.6 L, p = 0.009); however, body size poorly predicted V in regression analyses (R2 < 0.20). A fixed estimate of V (75 L) or use of 0.52 L/kg by total body weight yielded similar bias and error in this population. Conclusion Results of the largest analysis of vancomycin V in class III obesity to date indicated that use of a fixed V value (75 L) and use of a TBW-based estimate (0.52 L/kg) for estimation of vancomycin V in patients with a BMI of ≥40.0 kg/m2 have similar bias. Two postdistribution vancomycin concentrations are needed to accurately determine patient-specific pharmacokinetic parameters, estimate AUC, and improve the precision of vancomycin dosing in this patient population.

Behavior of fetal longitudinal myocardial fibers assessed by speckle tracking to obtain strain and strain rate values for low-risk pregnancies

2020 ◽  
Vol 48 (2) ◽  
pp. 144-152
Author(s):  
Mariana Biancardi ◽  
Renato Augusto Moreira de Sa
Keyword(s):  
Strain Rate ◽  
Gestational Age ◽  
Speckle Tracking ◽  
Age Groups ◽  
Cross Sectional Study ◽  
Observer Agreement ◽  
Cross Sectional ◽  
Strain And Strain Rate ◽  
Significant Difference ◽  
Myocardial Fibers

AbstractObjectiveTo analyze the behavior of fetal longitudinal myocardial fibers assessed by speckle tracking (STE) after fetal viability.MethodsA cross-sectional study was performed in 156 women with normal singleton pregnancies from 22 to 31 weeks of gestation. Strain (S) and strain rate (SR) values were measured in both ventricles during the fetal cardiac cycle. The population was divided into five gestational age groups based on 2-week intervals. The correlations of maternal variables with the S and SR variables and intra-observer analysis were performed.ResultsThere was a significant difference in the S and SR values of the left ventricle (LV) among the gestational age groups (P = 0.007). Significantly higher S and SR values were observed in early age groups demonstrating reductions in LV S and SR values at 26 weeks, followed by stabilization. For the right ventricle (RV), there was no significant difference between gestational age groups. Significant intra-observer agreement was observed for S values of the RV (P = 0.008) and LV (P = 0.0004) and SR values of the RV (P = 0.0001) and LV (P = 0.015).ConclusionDecreases in the S and SR values of the LV occurred after 26 weeks, followed by stabilization. No significant difference was observed in the S or SR value of the RV among the gestational age groups, and no significant association of any maternal variable evaluated with S and SR values was observed. Significant intra-observer agreement was obtained among the results.

scholarly journals Structural and Functional Changes in Maternal Heart during Pregnancy: An Echocardiographic Study

2017 ◽  
Vol 02 (04) ◽  
pp. 072-076
Author(s):  
Sunanda Kasula ◽  
Sumalatha Beeram ◽  
Ramakrishna Janapati ◽  
Indrani Garre
Keyword(s):  
Blood Pressure ◽  
Gestational Age ◽  
Systolic Function ◽  
Interventricular Septum ◽  
Clinical History ◽  
Left Ventricular ◽  
Two Dimensional ◽  
Cross Sectional ◽  
Functional Changes ◽  
Significant Difference

Abstract Background Pregnancy is associated with profound physiologic alterations in the maternal cardiovascular system. This study aimed to investigate maternal cardiac performance during normal pregnancy by two-dimensional echocardiography parameters and various functional and structural alterations. Methods This was a cross-sectional study of 100 normal pregnant women who attended the antenatal clinic, and all participants had clinical history, physical examination, and 12-lead electrocardiogram. Two-dimensional, M-mode, and Doppler echocardiography was done. Echocardiographic parameters were compared with normal age-matched controls from previously published studies. Results The mean age of the study group was 23.35 ± 3.05 years, mean systolic blood pressure was 110.5 ± 8.69 mm Hg, and mean diastolic blood pressure was 71.6 ± 6.77 mm Hg. There was an increase in left atrial (LA) diameter, left ventricular end diastolic diameter, and interventricular septum (IVS) thickness as gestational age advanced. There was a gradual decrease in E-wave velocity, and E/A ratio increased during the second trimester and decreased during the third trimester. The E-wave deceleration time increased with gestational age There was no statistically significant difference between IVS thickness and E/A ratio (p = 1.000). Conclusion Cardiac chamber dimensions, LV wall thickness, and LA size, most indices of systolic function although within normal range, were significantly higher in pregnant Asian Indian women than in the controls. This study shows that the subtle reduction in myocardial compliance appears as an adaptive response to changes of preload, afterload, and LV geometry.

Pharmacokinetics of Intermittent Intraperitoneal Cefazolin in Continuous Ambulatory Peritoneal Dialysis Patients

1999 ◽  
Vol 19 (1) ◽  
pp. 65-70 ◽  
Author(s):  
Harold J. Manley ◽  
George R. Bailie ◽  
Rupesh D. Asher ◽  
George Eisele ◽  
Reginald F. Frye
Keyword(s):  
Body Weight ◽  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Rate Constant ◽  
Half Life ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
Number Of Patients ◽  
The Mean ◽  
Concentration Levels

Objective To investigate the pharmacokinetic parameters of intermittent intraperitoneal (IP) cefazolin, and recommend a cefazolin dosing regimen in continuous ambulatory peritoneal dialysis (CAPD) patients. Design Prospective nonrandomized open study. Setting CAPD outpatient clinic in Albany, New York. Patients Seven volunteer CAPD patients without peritonitis. Three of the patients were nonanuric while 4 were anuric. Interventions Cefazolin (15 mg/kg total body weight) was given to each patient during the first peritoneal exchange. Blood and dialysate samples were collected at times 0, 0.5, 1, 2, 3, 6 (end of the first antibiotic-containing dwell), 24, and 48 hours after the administration of IP cefazolin. Urine samples were collected in nonanuric patients over the study period. Results The mean ± SD amount of cefazolin dose absorbed from the dialysate after the 6-hour dwell was 69.7% ± 8.0% of the administered dose. The cefazolin absorption rate constant from dialysate to serum was 0.21 ± 0.1 /hr (absorption half-life 3.5 ± 0.8 hr). The mean serum concentrations reached at 24 and 48 hours were 52.4 ± 3.7 mg/L and 30.3 ± 5.9 mg/L, respectively. The mean dialysate cefazolin concentrations reached at 24 and 48 hours were 15.1 ± 3.4 mg/L and 7.9 ± 1.4 mg/L, respectively. The cefazolin serum elimination rate constant was 0.02 ± 0.01 /hr (elimination half-life 31.5 ± 8.8 hr). The total cefazolin body clearance was 3.4 ± 0.6 mL/min. In the 3 nonanuric patients the mean renal clearance of cefazolin was 0.6 ± 0.4 mL/min. The peritoneal clearance of cefazolin was 1.0 ± 0.3 mL/min. The systemic volume of distribution of cefazolin was 0.2 ± 0.05 L/kg. No statistical difference was detected in pharmacokinetic parameters between anuric and nonanuric patients, although this may be due to the small number of patients in each group. Conclusion A single daily dose of cefazolin dosed at 15 mg/kg actual body weight in CAPD patients is effective in achieving serum concentration levels greater than the minimum inhibitory concentration for sensitive organisms over 48 hours, and dialysate concentration levels over 24 hours. Caution is warranted in extrapolation of dosing recommendations to patients who maintain a significant degree of residual renal function.

Population Pharmacokinetics of Cyclophosphamide in Patients with Thalassaemia Major Undergoing HSCT Shows Body Weight, CYP450, GST and ALDH Polymorphisms as Covariates Explaining Inter-Individual Variation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1182-1182 ◽  
Author(s):  
Poonkuzhali Balasubramanian ◽  
John Carl Panetta ◽  
Salamun Desire ◽  
Shaji R Velayudhan ◽  
Vikram Mathews ◽  
...  
Keyword(s):  
Body Weight ◽  
Individual Variation ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
Thalassaemia Major ◽  
Hematopoietic Stem ◽  
Beta Thalassaemia ◽  
Population Pk

Abstract Abstract 1182 Poster Board I-204 Cyclophosphamide (Cy) in combination with busulfan is an important component of myeloablative conditioning regimen used prior to hematopoietic stem cell transplantation (HSCT) for both malignant and non-malignant conditions. We have previously reported up to 20 fold inter-individual variation in the pharmacokinetics (PK) of Cy in patients with beta thalassaemia undergoing HSCT [Blood (ASH Annual Meeting Abstracts), Nov 2004; 104: 99]. PK parameters of Cy have been shown to be associated with regimen related toxicity and outcome of transplant. To explain the basis of the inter-individual variation in Cy PK, we have developed a population PK model. We analyzed the PK of Cy in consecutive children with beta thalassaemia major who received HSCT from HLA identical matched sibling donor at the Christian Medical College, Vellore from 2001 till 2004. A total of 900 cyclophosphamide concentration measurements from 55 patients were included and correlated with age, sex, body weight and 10 polymorphisms in enzymes involved in the metabolism or biotransformation of Cy namely GST A1, M1, T1, P1, CYP2B6, CYP2C9, CYP2C19 and ALDH genes. Non-linear mixed effects modeling analysis was performed with Monolix (version 2.4, www.monolix.org) to investigate the effect of patient covariates on PK, and to estimate the relative magnitude of inter-individual and inter-occasion variability. A two-compartment pharmacokinetic model was used to describe the data. The pharmacokinetic parameters estimated included elimination rate constant and volume (ke (1/hr), V (L or L/kg)), and the inter-compartmental parameters (k12 and k21 (1/hr)). The distribution of the parameters was assumed log-normal. Body weight was the main covariate which explained the largest portion of the IIV (28% and 20% of V and ke IIV, respectively). In addition, the following genotypes showed differences in the pharmacokinetics: GSTP1*B (1.7X higher ke in MUT versus WT or HET; p<0.05), CYP3A4*1B (2X higher ke in HET versus WT; p<0.05), and ALDH1A1*2 (2X higher ke in HET versus WT; p<0.05). We have developed a population PK model for Cy in thalassaemic children by considering morphological and biological covariates, which explains more than 45% and 22% (V and ke IIV, respectively) of the variation in Cy PK in these patients. This model-based algorithm may be used to design and plan targeted dose therapy in this group of pediatric patients and to predict the risk of toxicity and outcome of HSCT. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Assessment of the influence of overweight and obesity on the development of prehypertension and hypertension in children aged 6-15

2021 ◽  
Vol 50 (4) ◽  
pp. 85-96
Author(s):  
Marijana Jandrić-Kočić
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Primary School ◽  
Children And Adolescents ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
Primary School Children ◽  
Cross Sectional ◽  
Significant Difference ◽  
Hypertension In Children

Introduction/Aim: 41 million children under the age of 5 and 340 million children and adolescents aged 5 to 19 are overweight or obese. Obesity in children and adolescents is the most important predictor of high blood pressure. The aim of the study was to examine the incidence of overweight and obesity in primary school children aged 6 to 15 years, as well as to examine the incidence of prehypertension and hypertension in children who were overweight and obese. Method: The study included 85 of 86 children from the Primary School "Krupa na Uni". Data were collected with the help of a questionnaire, while body weight and blood pressure were measured. The chi-square test and t-test were used for the statistical analysis of data Results: The cross-sectional study included 85 children, 45 (52.9%) boys and 40 (47.1%) girls with an average age of 10.87 ± 2.70 years. Normal weight was found in 54 (63.5%) subjects, underweight in 12 (14.1%), overweight in 5 (5.9%), and obesity in 14 (16.5%). 76 (89.4%) subjects had normal blood pressure values, 5 (5.9%) prehypertensive state, and 4 (4.7%) arterial hypertension. There was no significant difference between younger and older children regarding their nutritional status (p=0.477) and blood pressure levels (p=0.453). Children who were overweight and obese had prehypertension and hypertension significantly more often (p˂0.001). Conclusion: Every fifth child was overweight or obese, while prehypertension or hypertension were found in every tenth child. The timely change of diet and physical activity could contribute to the regulation of body weight and the regulation of blood pressure, as well.

scholarly journals Transverse cerebellar diameter: a reliable predictor of gestational age

2020 ◽  
Vol 20 (4) ◽  
pp. 1927-32
Author(s):  
Sanjay Mishra ◽  
Surajit Ghatak ◽  
Pratibha Singh ◽  
Dushyant Agrawal ◽  
Pawan Garg
Keyword(s):  
Gestational Age ◽  
Indian Population ◽  
Cross Sectional Study ◽  
Abdominal Circumference ◽  
Sectional Study ◽  
Ethnic Population ◽  
Cross Sectional ◽  
Femur Length ◽  
Biparietal Diameter ◽  
Significant Difference

Objectives: To determine accuracy of transverse cerebellar diameter (TCD) measurement in the prediction of gestational age (GA) in normal fetuses; to develop reference chart for TCD according to GA in Indian population. Design: A retrospective cross-sectional study. Method: Ultrasonographic measurements in 300 singleton pregnant women included biparietal diameter (cm), head circum- ference (cm), abdominal circumference (cm), femur length (cm) and transverse cerebellar diameter (cm). Reference chart with mean TCD for corresponding gestational age (GA) in weeks was developed. Results: Statistically significant relationship found between TCD and gestational age (R2=0.92, p=0.0006). Regression for- mulae based on TCD with other parameter can be used to predict gestational age of foetus. When TCD is compared with findings in other studies in different ethnic population, it is found that there is significant difference exists. Conclusion: In normally developing fetuses the TCD has linear correlation with advancing gestational age. A separate refer- ence chart is required for every different population because ethnicity, nutrition and environmental factors can have impact on normal TCD values. This will help to avoid misinterpretation of data to determine gestational age. Keywords: Transverse cerebellar diameter; ultrasonography; gestational age.

scholarly journals Difference in The Incidence Severe Preeclampsia and Eclampsia between Maternal Age 20-34 Years and >34 Years in dr. Soebandi Hospital Jember

2017 ◽  
Vol 3 (2) ◽  
pp. 18
Author(s):  
Muhammad Fakhri Ali ◽  
Yonas Hadisubroto ◽  
Jauhar Firdaus
Keyword(s):  
Data Analysis ◽  
Mortality Rate ◽  
Maternal Mortality ◽  
Gestational Age ◽  
Maternal Age ◽  
Advanced Maternal Age ◽  
Severe Preeclampsia ◽  
Cross Sectional ◽  
Maternal Mortality Rate ◽  
Significant Difference

Maternal Mortality Rate (MMR) in Indonesia is still high. The maternal mortality rate continues to rise due to hypertension, one of which is caused by pre-eclampsia and eclampsia. Many factors cause preeclampsia, including advanced maternal age. The purpose of this study was to determine the effect of advanced maternal age during pregnancy with severe preeclampsia and eclampsia in RSD dr. Soebandi Jember. This study used cross sectional approach using 264 samples were divided into two groups, there are pregnant women aged 20-34 years and >34 years. The results of data analysis using Chi Square for severe preeclampsia and obtained p = 0.015 and OR = 2.494, which means there is a significant difference in comparison severe preeclampsia between gestational age of 20-34 years and >34 years. At the age of 20-34 years from 216 samples found 28 people suffering from severe preeclampsia (12.9%). Whereas at the age of mother> 34 years of 48 people found 13 people (27.1%) suffered severe preeclampsia Results of data analysis obtained eclampsia using Fisher and p = 0.554, which means there are no significant differences in comparison eclampsia between gestational age of 20-34 years and >34 years. At the age of 20-34 years from 216 samples found 3 people suffering from eclampsia (1.38%). While at mother age> 34 years from 48 people found 1 person (2.08%) suffered eclampsia.

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