Evaluation of Intravenous Posaconazole Dosing and Pharmacokinetic Target Attainment in Pediatric Patients

2018 ◽  
Vol 8 (4) ◽  
pp. 365-367 ◽  
Author(s):  
Jenna R Nickless ◽  
Kathryn E Bridger ◽  
Surabhi B Vora ◽  
Adam W Brothers

Abstract Limited data exist on intravenous (IV) posaconazole dosing and the risk for hepatotoxicity it confers to children. In this study, we evaluated dosing and resulting trough levels in 10 pediatric patients on IV posaconazole. A therapeutic level in these patients was achieved 95% of the time. We found a median minimum effective dose of 6.55 mg/kg of body weight. No correlation was found between the duration or posaconazole trough level and an increased alanine transaminase level.

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S548-S549
Author(s):  
Grant Stimes ◽  
Jennifer E Girotto ◽  
Joshua D Courter

Abstract Background Daptomycin (DAP) is lipopeptide that frequently is used to treat infections caused by Staphylococcus aureus in adult patients. There are limited data using daptomycin in pediatric patients for the treatment of osteomyelitis caused by S. aureus. This study’s objective is to describe pharmacodynamic (PD) target attainment of daptomycin in pediatric patients with osteomyelitis. Methods Medline was queried to obtain PD targets, pediatric pharmacokinetic models, and bone penetration information to build a model for DAP. A 10,000 subject Monte Carlo simulation was performed to estimate steady-state concentrations in the bone. Simulations modeled 30-minute infusions with using 12 mg/kg/dose IV q24h for patients less than 7 years and 10 mg/kg/dose IV q24h for patients 7 years and older. Goal PD targets were: AUC24: MIC of 666 μg hours/mL for log1 killing and AUC24: MIC of 1,061 for log2 killing. The CLSI breakpoint of 1 mg/L was used as a starting point and MIC’s were analyzed below that level. Results PD target attainment in percentages is listed for DAP below in Tables 1 and 2 and are separated by age groups of patients. Conclusion The studied DAP doses did not reach any PD target attainment at the CLSI breakpoint of 1 mg/L. Based on these data, DAP should not be empirically used to treat SA osteomyelitis unless the exact MIC is known. Furthermore, modern pediatric pharmacokinetic studies of DAP for pediatric osteomyelitis are warranted. Disclosures All authors: No reported disclosures.


2008 ◽  
Vol 191 (5) ◽  
pp. 1589-1594 ◽  
Author(s):  
Kyongtae T. Bae ◽  
Amisha J. Shah ◽  
Sherry S. Shang ◽  
Jin Hong Wang ◽  
Samuel Chang ◽  
...  

2021 ◽  
Vol 8 ◽  
pp. 2333794X2199034
Author(s):  
Phatthranit Phattharapornjaroen ◽  
Yuwares Sittichanbuncha ◽  
Pongsakorn Atiksawedparit ◽  
Kittisak Sawanyawisuth

Pediatric emergency patients are vulnerable population and require special care or interventions. Nevertheless, there is limited data on the prevalence and risk factors for life-saving interventions. This study is a retrospective analytical study. The inclusion criteria were children aged 15 years or under who were triaged as level 1 or 2 and treated at the resuscitation room. Factors associated with LSI were executed by logistic regression analysis. During the study period, there were 22 759 ER visits by 14 066 pediatric patients. Of those, 346 patients (2.46%) met the study criteria. Triage level 1 accounted for 16.18% (56 patients) with 29 patients (8.38%) with LSI. Trauma was an independent factor for LSI with adjusted odds ratio (95% CI) of 4.37 (1.49, 12.76). In conclusion, approximately 8.38% of these patients required LSI. Trauma cause was an independent predictor for LSI.


TH Open ◽  
2021 ◽  
Vol 05 (01) ◽  
pp. e84-e88
Author(s):  
Krishnan Shyamkumar ◽  
Jack Hirsh ◽  
Vinai C. Bhagirath ◽  
Jeffrey S. Ginsberg ◽  
John W. Eikelboom ◽  
...  

Abstract Introduction Dose adjustment based on laboratory monitoring is not routinely recommended for patients treated with rivaroxaban but because an association has been reported between high drug level and bleeding, it would be of interest to know if measuring drug level once could identify patients at risk of bleeding who might benefit from a dose reduction. Objective This study was aimed to investigate the reliability of a single measurement of rivaroxaban level to identify clinic patients with persistently high levels, defined as levels that remained in the upper quintile of drug-level distribution. Methods In this prospective cohort study of 100 patients with atrial fibrillation or venous thromboembolism, peak and trough rivaroxaban levels were measured using the STA-Liquid Anti-Xa assay at baseline and after 2 months. Values of 395.8 and 60.2 ng/mL corresponded to the 80th percentile for peak and trough levels, respectively, and levels above these cut-offs were categorized as high for our analyses. Results Among patients with a peak or trough level in the upper quintile at baseline, only 26.7% (95% confidence interval [CI]: 10.9–52.0%), and 13.3% (95% CI: 2.4–37.9%), respectively, remained above these thresholds. Conclusion Our findings do not support the use of a single rivaroxaban level measurement to identify patients who would benefit from a dose reduction because such an approach is unable to reliably identify patients with high levels.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Adam Jacobson ◽  
Carin Rojas ◽  
Brenda L. Bohnsack

Abstract Background Limited data exists on the effectiveness of the collagen matrix, Ologen, on increasing Ahmed glaucoma valve (AGV) success in childhood glaucomas. Methods Ocular examination and surgical details of pediatric patients who underwent AGV placement ± Ologen augmentation between 2012 and 2020. Complete success was defined as intraocular pressure (IOP) between 5 and 20 mmHg without glaucoma medications and additional IOP-lowering surgeries. Qualified success was defined as above, except IOP control maintained with or without glaucoma medications. Results Twenty-two eyes of 16 patients underwent AGV placement of which 6 eyes had Ologen-augmentation (OAGV) and 16 eyes had conventional surgery (CAGV). Average age was 6.4 ± 5.1 years with 4.2 ± 2.5 follow-up years. There was no difference in age, number of previous surgeries, and preoperative IOP and glaucoma medications. At final follow-up, success rate was 100% (5 eyes complete, 6 eyes qualified) in the OAGV group compared to 31% (0 eyes complete, 5 eyes qualified) in the CAGV group. One and two-year survival rates were 100% for OAGV compared to 62 and 38% for CAGV. Postoperative IOP was significantly lower at 1-month and final follow-up (p = 0.02) as was the number of glaucoma medications at 3, 6, 12-months and final follow-up (p < 0.05) in the OAGV group. Conclusions Ologen-augmentation increased the success and survival rates of AGVs in childhood glaucomas. Further, Ologen mitigated the hypertensive phase and decreased medication dependency. Longer follow-up with a greater number of eyes is required to fully evaluate the effectiveness of OAGV.


Author(s):  
Zhaoyang Li ◽  
Barbara McCoy ◽  
Werner Engl ◽  
Leman Yel

AbstractPatients with primary immunodeficiency diseases often require lifelong immunoglobulin (IG) therapy. Most clinical trials investigating IG therapies characterize serum immunoglobulin G (IgG) pharmacokinetic (PK) profiles by serially assessing serum IgG levels. This retrospective analysis evaluated whether steady-state serum IgG trough level measurement alone is adequate for PK assessment. Based on individual patient serum IgG trough levels from two pivotal trials (phase 2/3 European [NCT01412385] and North American [NCT01218438]) of weekly 20% subcutaneous IG (SCIG; Cuvitru, Ig20Gly), trough level-predicted IgG AUC (AUCτ,tp) were calculated and compared with the reported AUC calculated from serum IgG concentration-time profiles (AUCτ). In both studies, mean AUCτ,tp values for Ig20Gly were essentially equivalent to AUCτ with point estimates of geometric mean ratio (GMR) of AUCτ,tp/AUCτ near 1.0 and 90% CIs within 0.80–1.25. In contrast, for IVIG, 10%, mean AUCτ,tp values were lower than AUCτ by >20%, (GMR [90% CI]: 0.74 [0.70–0.78] and 0.77 [0.73–0.81] for the two studies, respectively). Mean AUCτ,tp values calculated for 4 other SCIG products (based on mean IgG trough levels reported in the literature/labels) were also essentially equivalent to the reported AUCτ (differences <10% for all except HyQvia, a facilitated SCIG product), while differences for IVIG products were >20%. In conclusion, steady-state serum IgG levels following weekly SCIG remain stable, allowing for reliable prediction of AUC over the dosing interval using trough IgG levels. These findings indicate that measuring steady-state serum IgG trough levels alone may be adequate for PK assessment of weekly SCIG.


2009 ◽  
Vol 29 (2) ◽  
pp. 231-236 ◽  
Author(s):  
Jung Il Lee ◽  
Hyun Joo Park ◽  
Jin Woo Lee ◽  
Young Soo Kim ◽  
Seok Jeong ◽  
...  

2010 ◽  
Vol 138 (1-2) ◽  
pp. 50-55 ◽  
Author(s):  
Biljana Pejovic ◽  
Milica Rankovic-Janevski ◽  
Niveska Bozinovic-Prekajski

Introduction. Drug safety depends on trough levels. Objective. Objective of the study was to measure gentamicin and amikacin trough levels in neonates and to identify risk groups by gestational and postnatal age. Methods. Gentamicin and amikacin were applied according to the clinical practice guidelines. Trough levels (mg/l) were deter- mined using fluorescence polarization immunoassay methodology. Target trough levels were <2 mg/l for gentamicin, and <10 mg/l for amikacin. Patients were divided in 3 groups by gestational age: I ?32, II 33-36, and III ?37 gestational weeks and, by postnatal age, in 2 groups: ?7 and >7 days. Results. Out of 163 neonates, 111 were receiving gentamicin and 52 amikacin. Mean amikacin trough level was 7.8?4.8 mg/l and, in group I 10.5?4.9 mg/l, which was above the target range and significantly higher than in group II (LSD, p<0.05). In the amikacin group, 26 patients were 7 and less, and 26 more than 7 days old, without significant differences in trough levels between the groups. In the gentamicin group, 52.3% of neonates had trough values within the target range. Gentamicin trough level in group I was above the trough range, 3.7?1.8, 2.3?1.5 in group II and, 1.8?1.4 mg/l in group III. The difference in trough levels among the groups was highly significant (F=9.015, p<0.001, ?2=17. 576, p<0.001). Further analysis revealed that differences between groups I and II (LSD, p=0.002) and between I and III (LSD, p=0.000) were highly significant. Conclusion. Obtained gentamicin and amikacin trough levels are high. Inverse correlation has been confirmed between trough level and gestational age, with highly significant difference, and the risk group has been identified. There is obviously a need to change the dosing regimen in terms of those with extended intervals, particularly for neonates of the lowest gestational age, along with pharmacokinetic measurements.


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