scholarly journals Dosing regimen of gentamicin and the effect of antenatal steroids on clearance in preterm infants

2019 ◽  
Author(s):  
Roberto P. Santos ◽  
Yin Chang ◽  
Carlos R. Oliveira ◽  
Beverly Adams-Huet ◽  
John Gard ◽  
...  
Keyword(s):  
Preterm Infants ◽  
Retrospective Cohort ◽  
Drug Exposure ◽  
Dosing Regimen ◽  
Once Daily ◽  
Target Drug ◽  
Antenatal Steroids ◽  
Antenatal Steroid ◽  
Trough Concentrations ◽  
Indomethacin Treatment

ABSTRACTObjectiveDetermine the gentamicin pharmacokinetic and pharmacodynamic (PK/PD) profiles of once daily dosing (ODD) versus every 18-hour (q18h) regimens and to characterize the effect of antenatal steroid on gentamicin clearance (GentCL).Study DesignRetrospective cohort of preterm infants (≤34 weeks gestation; ≤7 days) who received gentamicin for >48 hours from January 2005 to June 2007. Serum gentamicin peak and trough concentrations were determined, and PK/PD profiles calculated using standard noncompartmental methods.Result122 (63%) infants received ODD and 73 (37%) received q18h regimen. Desired gentamicin peak (5 to 12 mcg/mL) and trough (<2 mcg/mL) concentrations were achieved in 80% (95%CI, 72-86) on ODD vs. 47% (95%CI, 36-58) on q18h (p<0.001). Target drug exposure (AUC >72 mcg/mL/hr) was achieved in 73% (89/122) of infants on ODD vs. 22% (16/73) on q18h (p < 0.001). GentCLwas significantly lower in those who receive antenatal steroid (37+/-8 mL/kg/hr vs. 42+/-13 mL/kg/hr,p=0.04)but not affected by postnatal indomethacin treatment (p>0.86).ConclusionPK/PD profile of gentamicin is improved by ODD in preterm infants. GentClwas significantly less in infants exposed to antenatal steroids but not in those treated with indomethacin.

scholarly journals An Evaluation of Twice-Daily Dosing of Caffeine for Apnea of Prematurity

2021 ◽  
Vol 26 (3) ◽  
pp. 253-257
Author(s):  
Aubrey Rebentisch ◽  
Karen Kovey ◽  
Sheri Denslow
Keyword(s):  
Retrospective Analysis ◽  
Preterm Infants ◽  
Maintenance Dose ◽  
Primary Outcome ◽  
Dosing Regimen ◽  
Once Daily ◽  
Caffeine Citrate ◽  
Apnea Of Prematurity

OBJECTIVE Preterm infants often require caffeine for the treatment of apnea. While the maintenance dose of caffeine citrate is usually administered once daily per FDA labeling, many providers administer the maintenance dose in two divided doses. This study evaluated the effectiveness of a twice daily dosing regimen of caffeine for apnea of prematurity. METHODS This was a retrospective analysis conducted from 2013–2018 that included preterm infants who received caffeine that was dosed both once and twice daily respectively. The primary outcome of our study was a composite of the number of apneic and bradycardic events for five 24-hour periods prior to switching to twice daily dosing of caffeine and five 24-hour periods after switching to twice daily dosing of caffeine. RESULTS The median five-day average incidence of apnea and bradycardia during the once and twice daily dosing periods was 6.2 events and 6.4 events respectively (p=0.09). CONCLUSIONS There is little benefit of twice daily dosing of caffeine for apnea of prematurity.

Improving incidence trends of severe intraventricular haemorrhages in preterm infants <32 weeks gestation: a cohort study

2019 ◽  
Vol 105 (2) ◽  
pp. 145-150 ◽  
Author(s):  
Kee Thai Yeo ◽  
Reji Thomas ◽  
Sharon SW Chow ◽  
Srinivas Bolisetty ◽  
Ross Haslam ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
New Zealand ◽  
Preterm Infants ◽  
Apgar Score ◽  
Intraventricular Haemorrhage ◽  
Population Based ◽  
Incidence Trends ◽  
Antenatal Steroids ◽  
Antenatal Steroid

ObjectiveTo describe the trend and risk factors for severe intraventricular haemorrhage (IVH) among infants <32 weeks gestation.DesignPopulation-based cohort study.SettingAustralia and New Zealand.PatientsAll preterm infants <32 weeks gestation in the Australian and New Zealand Neonatal Network (ANZNN) from 1995 to 2012.InterventionsComparison of IVH incidence between 6-year epochs.Main outcome measuresOverall IVH and severe IVH incidence.ResultsA total of 60 068 infants were included, and overall survival to discharge increased from 89% to 93% over the three epochs. As the percentage of infants with IVH decreased from 23.6% to 21.3% and 21.4% (p<0.001) from epoch 1 to 3, respectively, fewer survivors had severe IVH (4.0%, 3.3% and 2.8%, respectively, p<0.001). Over time, there were fewer antenatal complications, higher antenatal steroid usage and more caesarean-section births. Fewer infants were intubated at birth, had low 5 min Apgar score, had sepsis or pneumothorax needing drainage. Adjusted for perinatal confounders, there was significant reduction in odds of severe IVH from epoch 1 to 3 (adjusted OR (AOR) 0.8, 95% CI 0.7 to 0.9). Factors associated with development of severe IVH include no antenatal steroids (AOR 1.7, 95% CI 1.5 to 1.9), male (AOR 1.3, 95% CI 1.2 to 1.4), 5 min Apgar score <7 (AOR 2.0, 95% CI 1.9 to 2.2), intubated at birth (AOR 2.0, 95% CI 1.8 to 2.2), extremely low gestational age (AOR 4.0, 95% CI 3.7 to 4.4), outborn (AOR 1.6, 95% CI 1.5 to 1.8) and vaginal delivery (AOR 1.4, 95% CI 1.3 to 1.6).ConclusionsAlong with increased survival among infants born <32 weeks gestation, the incidence of severe IVH has decreased over the 18 years, especially in the most recent period. This coincided with reduction in rates of risk factors for severe IVH development.

Evaluation of Low-Dose Gentamicin Once Daily Dosing Regimen at A General Hospital in Malaysia

2018 ◽  
Vol 9 (01) ◽  
Author(s):  
Ab Rahman A F ◽  
Md Sahak N. ◽  
Ali A. M.
Keyword(s):  
Medical Records ◽  
Public Hospital ◽  
Low Dose ◽  
Dosing Regimen ◽  
Once Daily ◽  
Neutropenic Sepsis ◽  
Wide Acceptance ◽  
The Mean ◽  
Initiation Of Therapy ◽  
Almost All

Objective: Once daily dosing (ODD) aminoglycoside is gaining wide acceptance as an alternative way of dosing. In our setting it is the regimen of choice whenever gentamicin is indicated. The objective of this study was to evaluate the practice of gentamicin ODD in a public hospital in Malaysia. Methods: We conducted a retrospective review of medical records of patients on gentamicin ODD who were admitted to Hospital Melaka during January 2002 until March 2010. All adult patients who were on ODD gentamicin with various level of renal function were included in the study. Patients on gentamicin less than 72 hours and pregnant women were excluded. Results: From 110 patients, 75 (68.2%) were male and 35 (31.8%) were female. Indications for ODD gentamicin included pneumonia, 34 (31.0%) neutropenic sepsis, 27 (24.5%) and sepsis, 11 (10.0%). The mean dose and duration of gentamicin was 3.2 mg/kg/day and 7 days, respectively. Almost all patients were on gentamicin combined with other antibiotics. Clinical cure based on fever resolution was found in 89.1% of patients treated with ODD. Resolution of fever took an average of 48 hours after initiation of therapy. The evaluation for bacteriologic cure could not be performed because of insufficient data on culture and sensitivity. Out of 38 patients with analyzable serum creatinine data, four patients might have developed nephrotoxicity. Conclusion: In our setting, lower dosages of ODD gentamicin when used in combination with other antibiotics seemed to be effective and safe in treating most gram negative infections.

Dose-dependent Pharmacological Response to Rituximab in the Treatment of Antineutrophil Cytoplasmic Antibody-Associated Vasculiti

2021 ◽  
pp. jrheum.210361
Author(s):  
Jason M. Springer ◽  
Ryan S. Funk
Keyword(s):  
B Cell ◽  
Antineutrophil Cytoplasmic Antibody ◽  
High Dose ◽  
Dosing Regimen ◽  
Dosing Interval ◽  
Cell Counts ◽  
Pharmacological Response ◽  
Trough Concentrations ◽  
Cell Repopulation ◽  
Trough Plasma

Objective Rituximab (RTX) is effective in induction and maintenance of remission in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). However, uncertainty remains regarding the optimal maintenance dosing regimen. This work evaluates the relationship between variability in RTX dosing and pharmacological response in AAV. Methods A prospective cohort of AAV patients (n=28) with either GPA (n=23) or MPA (n=5) receiving maintenance RTX therapy were followed in a single tertiary care academic medical center over a 2-year period. Patient demographics, RTX dosing information, and trough plasma RTX levels were collected along with laboratory measures of pharmacologic response, including B-cell counts and ANCA titers. Results RTX dosing information from 94 infusions with 59 trough samples were collected with a mean±SD dose of 640±221 mg, dosing interval of 210±88 days, and trough plasma RTX concentration of 622±548 ng/mL. RTX trough concentrations were associated with RTX dose (ρ=0.60, p<0.0001) and dosing interval (ρ=-0.55, p<0.0001). RTX dosing intensity (mg/d) was associated with RTX trough concentrations (ρ=0.57, p<0.0001). Higher dosing intensities were associated with undetectable B-cell repopulation (p<0.0001), but not negative ANCA titers (p=0.6). Stratification of dosing intensities based on the standard dosing regimen of 500 mg every six months (2.4 to 3.3 mg/d) demonstrated that this regimen was associated with B-cell repopulation in 8 of 17 doses (47%) compared to 0 of 23 doses (0%) with the high-dose regimen (>3.3 mg/d) (p<0.0001). Conclusion RTX maintenance dosing of 500 mg every six months may be inadequate to maintain B-cell depletion in the treatment of AAV.

Clinical pharmacokinetics of bdtx-189, an inhibitor of allosteric ErbB mutations, in patients with advanced solid malignancies in MasterKey-01 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3097-3097
Author(s):  
Nigel Waters ◽  
Manish R. Patel ◽  
Alison M. Schram ◽  
Jordi Rodon Ahnert ◽  
Shekeab Jauhari ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Drug Exposure ◽  
Target Range ◽  
Dosing Regimen ◽  
High Fat ◽  
Clinical Pharmacokinetics ◽  
Median Tmax ◽  
Fasted State ◽  
Rapid Absorption ◽  
Fat Meal

3097 Background: Allosteric oncogenic mutations occur outside the canonical ATP-binding site of EGFR and HER2, and there are no approved therapies that target such mutations. BDTX-189 is a potent, selective, irreversible inhibitor of 48 allosteric EGFR and HER2 mutant variants under clinical evaluation in the ongoing MasterKey-01 trial (NCT04209465). BDTX-189 was designed to rapidly and irreversibly occupy the active site of targeted ErbB mutants, leading to sustained pharmacodynamic (PD) effects, and with selectivity over EGFR-WT in order to minimize EGFR-WT mediated toxicities. The pharmacokinetic (PK) profile was designed for rapid absorption and fast elimination to maintain target occupancy while minimizing prolonged drug exposure that could contribute to off-target associated toxicities. Methods: In MasterKey-01, BDTX-189 was administered orally once daily in continuous 21-day cycles, taken fasted. Dose escalation included cohorts of 1-2 patients receiving doses between 25 and 200 mg QD followed by 5-7 patients receiving 400 mg, 800 mg, or 1,200 mg QD fasted. The possible effects of a high fat meal on the PK of BDTX-189 were assessed in a subset of patients receiving single doses of 400 mg BDTX-189 fasted and immediately after a high-fat breakfast in a randomized crossover fashion with 3 days between doses. In addition, a dose escalation cohort investigating administration of BDTX-189 non-fasted was enrolled at 800 mg QD. Serial blood samples for analysis of plasma BDTX-189 concentrations were collected after each dose on C1D1 and C1D15. BDTX-189 levels were determined using LC-MS, and data analyzed using non-compartmental methods. Results: After single and multiple doses, BDTX-189 was rapidly absorbed (median tmax 1-2 h), with an elimination t1/2 of 2-6 h. Dose-dependent increases in exposure from 200 to 800 mg QD fasted were observed, with no apparent accumulation or decline in exposures observed at steady-state. Administration of BDTX-189 with a high-fat meal increased AUC approximately 1.7-fold with minimal effect on Cmax, relative to administration in the fasted state. At 800 mg QD, mean AUC was similar in the non-fasting state relative to fasting and was within the target efficacious range defined by mouse models harboring allo-ErbB mutated tumors. Median tmax and t1/2 values were similar after administration in the non-fasted and fasted states. Conclusions: BDTX-189 demonstrated rapid absorption and a short PK half-life consistent with the desired PK/PD profile, with exposures in the efficacious target range based on preclinical data. The pilot high fat food-effect data and non-fasting QD dosing regimen show similar or improved systemic exposure relative to dosing in the fasted state. The MasterKey-01 trial is ongoing, including refinement of the dosing regimen and identification of the recommended phase 2 dose. Clinical trial information: NCT04209465.

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