What is the Best Predictor of Phenobarbital Pharmacokinetics to Use for Initial Dosing in Neonates?

Phenobarbital is a first-line treatment of various seizure types in newborns. Dosage individualization maximizing the proportion of patients with drug levels in therapeutic range or sufficient treatment response is still challenging. The aim of this review was to summarize the available evidence on phenobarbital pharmacokinetics in neonates and to identify its possible covariates suitable for individualization of initial drug dosing. Several covariates have been considered: body weight and height, body surface area, gestational and postnatal age, laboratory parameters of renal and hepatic functions, asphyxia, therapeutic hypothermia, extracorporeal membrane oxygenation (ECMO), drug interactions, and genetic polymorphisms. The most frequently studied and well-founded covariate for the estimation of phenobarbital dosing is actual body weight. Loading dose of 15–20 mg/kg followed by a maintenance dose of 3–5 mg/kg/day seems to be accurate. However, the evidence for the other covariates with respect to dosing individualization is not sufficient. Doses at the lower limit of suggested range should be preferred in patients with severe asphyxia, while the upper limit of the range should be targeted in neonates receiving ECMO support.

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d4T: keep it or abandon it?

Asian Biomedicine ◽

10.2478/abm-2010-0068 ◽

2010 ◽

Vol 4 (4) ◽

pp. 541-546 ◽

Cited By ~ 1

Author(s):

Andrew Hill

Keyword(s):

Body Weight ◽

Adverse Events ◽

World Health ◽

Nucleoside Analogues ◽

Line Treatment ◽

First Line ◽

The World ◽

Dose Ranging ◽

Health Organization ◽

First Line Treatment

Abstract Stavudine is a nucleoside analogue used widely for first-line treatment of HIV in developing and middleincome countries. The World Health Organization recommended that all patients should switch to stavudine (30mg BID). However, there is evidence from the dose-ranging trials that patients with body weight below 60kg should use a dose of 20mg BID. For patients who show adverse events on stavudine, a switch to other nucleoside analogues can be considered. This article reviews d4T to study if it should be kept or abandoned.

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Vancomycin Adult Dosing and Monitoring

10.1093/med/9780199797783.003.0017 ◽

2012 ◽

Author(s):

John W. Wilson ◽

Lynn L. Estes

Keyword(s):

Health Care ◽

Body Weight ◽

Renal Replacement Therapy ◽

Serum Levels ◽

Loading Dose ◽

Actual Body Weight ◽

Serious Infections ◽

The One ◽

Monitoring Protocols ◽

Health Care Associated Pneumonia

(Note: Several vancomycin dosing and monitoring protocols exist; this is the one used at Mayo Clinic.)•Loading dose: Consider 20–30 mg/kg, especially in critically ill patients with serious infections such as meningitis, health care–associated pneumonia, or endocarditis.•Maintenance dose: Give 15–20 mg/kg based on actual body weight for most patients (20 mg/kg is reasonable when aiming for a trough range of 15–20 mcg/mL). Adjust based on serum levels. See also the following sections on hemodialysis and continuous renal replacement therapy....

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Intravenous immunoglobulins as first-line treatment in idiopathic inflammatory myopathies: a pilot study

Rheumatology ◽

10.1093/rheumatology/keaa459 ◽

2020 ◽

Author(s):

Johan Lim ◽

Filip Eftimov ◽

Camiel Verhamme ◽

Esther Brusse ◽

Jessica E Hoogendijk ◽

...

Keyword(s):

Body Weight ◽

Rescue Medication ◽

Inflammatory Myopathy ◽

Idiopathic Inflammatory Myopathy ◽

Line Treatment ◽

First Line ◽

Serious Adverse Events ◽

Moderate Improvement ◽

Number Of Patients ◽

First Line Treatment

Abstract Objectives We explored efficacy and safety of IVIg as first-line treatment in patients with an idiopathic inflammatory myopathy. Methods In this investigator-initiated phase 2 open-label study, we included 20 adults with a newly diagnosed, biopsy-proven idiopathic inflammatory myopathy, and a disease duration of less than 9 months. Patients with IBM and prior use of immunosuppressants were excluded. The standard treatment regimen consisted of IVIg (Privigen) monotherapy for 9 weeks: a loading dose (2 g/kg body weight) and two subsequent maintenance doses (1 g/kg body weight) with a 3-week interval. The primary outcome was the number of patients with at least moderate improvement on the 2016 ACR/EULAR Total Improvement Score. Secondary outcomes included time to improvement, the number of patients requiring rescue medication and serious adverse events. Results We included patients with DM (n = 9), immune-mediated necrotizing myopathy (n = 6), non-specific myositis/overlap myositis (n = 4) and anti-synthetase syndrome (n = 1). One patient was excluded from analyses because of minimal weakness resulting in a ceiling effect. Eight patients (8/19 = 42.0%; Clopper–Pearson 95% CI: 19.6, 64.6) had at least moderate improvement by 9 weeks. Of these, six reached improvement by 3 weeks. Seven patients required rescue medication due to insufficient efficacy and prematurely ended the study. Three serious adverse events occurred, of which one was pulmonary embolism. Conclusion First-line IVIg monotherapy led to at least moderate improvement in nearly half of patients with a fast clinical response in the majority of responders. Trial registration Netherlands Trial Register identifier, NTR6160.

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Levetiracetam optimal dose-finding as first-line treatment for neonatal seizures occurring in the context of hypoxic-ischaemic encephalopathy (LEVNEONAT-1): study protocol of a phase II trial

BMJ Open ◽

10.1136/bmjopen-2018-022739 ◽

2019 ◽

Vol 9 (1) ◽

pp. e022739 ◽

Cited By ~ 7

Author(s):

Geraldine Favrais ◽

Moreno Ursino ◽

Catherine Mouchel ◽

Estelle Boivin ◽

Vincent Jullien ◽

...

Keyword(s):

Dose Level ◽

Phase Ii ◽

Phase Ii Trial ◽

Optimal Dose ◽

Dose Finding ◽

Loading Dose ◽

Line Treatment ◽

Neonatal Seizures ◽

First Line ◽

First Line Treatment

IntroductionTherapeutic schedules for treating neonatal seizures remain elusive. First-line treatment with phenobarbital is widely supported but without strong scientific evidence. Levetiracetam (LEV) is an emerging and promising antiepileptic drug (AED). The aim of this phase II trial is to determine the benefits of LEV by applying a strict methodology and to estimate the optimal dose of LEV as a first-line AED to treat seizures in newborns suffering from hypoxic-ischaemic encephalopathy.Methods and analysisLEVNEONAT-1 is an open and sequential LEV dose-finding study. The optimal dose is that which is estimated to be associated with a toxicity not exceeding 10% and an efficacy higher than 60%. Efficacy is defined by a seizure burden reduction of 80% after the loading dose. Four increasing dose regimens will be assessed including one loading dose of 30, 40, 50 or 60 mg/kg followed by eight maintenance doses (ie, a quarter of the loading dose) injected every 8 hours. A two-patient cohort will be necessary at each dose level to consider an upper dose level assignment. The maximal sample size expected is 50 participants with a minimum of 24 patients or fewer in the case of a high rate of toxicity. Patients will be recruited in five neonatal intensive care units beginning in October 2017 and continuing for 2 years. In parallel, the LEV pharmacokinetics will be measured five times (ie, 30 min; 4 and 7 hours after the loading dose; 1–3 hours and 12–18 hours after the last maintenance dose).Ethics and disseminationEthics approval has been obtained from the regional ethical committee (2016-R25) and the French Drug Safety Agency (160652A-31). The results will be published in a peer-reviewed journal. The results will also be presented at medical meetings.Trial registration numberNCT02229123; Pre-results.

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Cost Analysis of Biologic Drugs in Rheumatoid Arthritis First Line Treatment After Methotrexate Failure According to Patients’ Body Weight

Reumatología Clínica (English Edition) ◽

10.1016/j.reumae.2015.07.006 ◽

2016 ◽

Vol 12 (3) ◽

pp. 123-129

Author(s):

José Andrés Román Ivorra ◽

José Ivorra ◽

Emilio Monte-Boquet ◽

Cristina Canal ◽

Itziar Oyagüez ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Body Weight ◽

Cost Analysis ◽

Line Treatment ◽

First Line ◽

Biologic Drugs ◽

First Line Treatment

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Frequency of Body Weight Loss is an Independent Prognostic Factor of First-Line Treatment Outcomes in Metastatic Colorectal Cancer

Nutrition and Cancer ◽

10.1080/01635581.2021.1900300 ◽

2021 ◽

pp. 1-7

Author(s):

Juraj Prejac ◽

Domina Kekez ◽

Borislav Belev ◽

Marija Prejac ◽

Stjepko Pleština

Keyword(s):

Colorectal Cancer ◽

Weight Loss ◽

Body Weight ◽

Prognostic Factor ◽

Metastatic Colorectal Cancer ◽

Treatment Outcomes ◽

Body Weight Loss ◽

Line Treatment ◽

First Line ◽

First Line Treatment

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Comparison of risperidone, olanzapine and quetiapine: effects on body weight, serum blood glucose and prolactin

International Psychiatry ◽

10.1192/s1749367600002125 ◽

2008 ◽

Vol 5 (3) ◽

pp. 71-73

Author(s):

Haroon Rashid Chaudhry ◽

Nadia Arshad ◽

Saima Niaz ◽

Tahir Suleman ◽

Khalid A. Mufti

Keyword(s):

Body Weight ◽

Blood Glucose ◽

Chronic Illness ◽

Economic Consequences ◽

Line Treatment ◽

First Line ◽

Antipsychotic Medications ◽

The Past ◽

Atypical Antipsychotic Medications ◽

First Line Treatment

Schizophrenia is a chronic illness with a lifetime prevalence of 1% and with serious physical, social and economic consequences. Over the past decade, atypical antipsychotic medications have become the first-line treatment for schizophrenia (Breier et al, 2005).

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Drug dosing in chronic kidney disease

10.1093/med/9780199592548.003.0363 ◽

2015 ◽

Cited By ~ 1

Author(s):

Ali J. Olyaei ◽

Ted A. Foster ◽

Edgar V. Lerma

Keyword(s):

Chronic Kidney Disease ◽

Renal Function ◽

Kidney Disease ◽

Systematic Approach ◽

Loading Dose ◽

Accurate Assessment ◽

Drug Dosing ◽

Drug Levels ◽

Monitoring Drug ◽

Drug Removal

This chapter is dedicated to the dosing of medications in patients with chronic kidney disease. It is important for clinicians to have a working understanding of basic pharmacokinetic and pharmacodynamic principles to ensure patients with chronic kidney disease achieve the therapeutic target without toxicity. This chapter will provide a systematic approach to medication dosing in patients with chronic kidney disease by obtaining a medical history and performing a thorough physical examination, calculating an accurate assessment of renal function, determining loading dose, determining a maintenance dose, and monitoring drug levels if indicated. Specific pharmacologic considerations in the setting of renal insufficiency along with drug removal by dialysis are also outlined.

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Sufficient and Timely Autologous Stem Cell Harvest After Chemoimmunotherapy with Alemtuzumab In Combination with Bi-Weekly CHOP as First Line Treatment In Systemic Peripheral T-Cell Lymphomas (PTCL): a Feasibility Analysis From the First Randomized Trial In Systemic PTCL (ACT trial)

Blood ◽

10.1182/blood.v116.21.2395.2395 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2395-2395

Author(s):

Francesco d'Amore ◽

Maria Gomes da Silva ◽

Sirpa Leppa ◽

Antonio Pezzutto ◽

Thomas Relander ◽

...

Keyword(s):

Body Weight ◽

Stem Cell ◽

T Cell ◽

Stem Cell Transplant ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

First Line ◽

Cd34 Cells ◽

Cell Harvest ◽

First Line Treatment

Abstract Abstract 2395 While already tested in T-PLL, the impact of chemo-immunotherapy with alemtuzumab in combination with bi-weekly CHOP on autologous stem cell harvest (ASCH) has not yet been analysed in the context of first line treatment of primary systemic peripheral T-cell lymphoma (PTCL). We therefore evaluated the feasibility of ASCH in the first 23 patients of the ongoing international multicenter ACT-1 study, the first, and so far only, randomized trial in primary systemic PTCL. The ACT trials (ACT-1 + ACT-2) test the addition of alemtuzumab to CHOP followed, in younger patients (ACT-1), by high-dose therapy with autologous stem cell transplant (HDT+ASCT). The aims of the analysis were: (i) feasibility of ASCH in alemtuzumab + CHOP (A-CHOP) treated patients as compared to patients not receiving the antibody, but otherwise treated and managed in the same way, and (ii) comparison of ASCH counts in the two treatment arms. By July 2010, 20 patients, 11 in the standard treatment (arm A) and 9 in the experimental treatment (arm B) cohort, had undergone induction therapy and had been primed for subsequent ASCH according to local guidelines. Histological subtype distribution in the two treatment groups showed: PTCL not otherwise specified N=4 (arm A) and N=5 (arm B), angioimmunoblastic N=5 (arm A) and N=4 (arm B), extranodal NK/T-cell, nasal type N=1 (arm A), hepatosplenic N=1 (arm A). Pre-therapeutic evidence of bone marrow involvement was present in 4 (arm A) and 2 (arm B) patients, respectively. Of the original 23 patients, three did not undergo stem-cell harvest due to progressive disease (1 pt), patient's decision (1 pt), and pre-therapeutic CNS involvement (1 pt). Among the 20 harvested patients, ASCH failure was experienced in three patients (standard arm N=1 and experimental arm N=2; p=0.57). In two patients (one in each treatment cohort) a suboptimal stem cell yield could be optimized by the use of plerixafor according to local guidelines. A comparison of stem cell counts (CD34+ cells × 106/kg body weight) from the two treatment cohorts showed a trend towards moderately lower stem cell yields in alemtuzumab-treated patients (3.34 CD34+ cells × 106/kg body weight in arm B vs 6.54 CD34+ cells × 106/kg body weight in arm A, p=0.03). In conclusion, the addition of alemtuzumab to bi-weekly CHOP in the setting of first-line therapy of primary systemic PTCL does not significantly impair ASCH prior to upfront autologous stem cell transplant. Disclosures: No relevant conflicts of interest to declare.

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The advantage of pemetrexed combined with platium chemotherapy treatement for advanced nonsquamous non-small-cell lung cancer (NSCLC) patients without drive oncogene.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e20527 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e20527-e20527

Author(s):

Haiyan Xu ◽

Yan Wang

Keyword(s):

Large Scale ◽

Objective Response ◽

Evaluation Criteria ◽

Progression Free Survival ◽

The Other ◽

Line Treatment ◽

First Line ◽

Platinum Based Chemotherapy ◽

Nsclc Patients ◽

First Line Treatment

e20527 Background:Platinum-based chemotherapy is the standard first-line treatment for non-squamous NSCLC patients without driver oncogene (EGFR, KRAS, and ALK mutations). However, it remains unknown that from which chemotherapy regimens can those patients get more benefit. Therefore, the study explore whether pemetrexed combined with platinum chemotherapy is superior to the other platinum-based chemotherapy regimens.Methods:We performed a retrospective study on 114 histologically or cytologically advanced IIIB-IV NSCLC patients admitted to Cancer Hospital from 1 Jan 2013 to 30 Dec 2015. The primary endpoint was the median progression free survival (PFS) and the disease control rate (DCR). And objective response was evaluated every two cycles by imaging according to the Response Evaluation Criteria In Solid Tumors (RECIST version 1.0). The multivariate logistic analyses were carried out by SPSS version 16.0. Results:114 patients received platinum-base doublet as first-line treatment. Among them, 59 patients underwent pemetrexed-containing regimens, and 55 patients received non-pemetrexed-containing regimens (38 patients for paclitaxel-containing regimens, 13 patients for gemcitabine-containing regimens, and 4 patients for other regimens.). The baseline characteristics between two groups were comparable ( p>0.05). The median PFS of pemetrexed-containing regimens was significantly longer compared with that of non-pemetrexed-containing regimens (7.2 months [95% CI: 5.3–9.1] vs. 4.9 months [95% CI: 3.2–6.6], p%0.05). DCR of pemetrexed-containing regimens was better than that of non-pemetrexed-containing regimens in the multivariate logistic analysis (89.8% vs.74.5%, p%0.05).Conclusions:Pemetrexed-containing regimens displayed more benefit than the other chemotherapy regimens for non-squamous NSCLC patients without driver oncogene. However, large scale perspective study is warranted in the future.

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