scholarly journals Intrathecal Riluzole for the Treatment of Patients With Amyotrophic Lateral Sclerosis

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Nicholas M Boulis
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Side Effects ◽  
Oral Administration ◽  
Oral Therapy ◽  
Drug Exposure ◽  
Oral Treatment ◽  
Oral Drug ◽  
Systemic Drug Exposure ◽  
Lateral Sclerosis ◽  
Systemic Drug

Abstract INTRODUCTION Oral riluzole is the only approved treatment known to improve survival in patients with amyotrophic lateral sclerosis (ALS), with modest efficacy and dosing limited by hepatic toxicity and asthenia. We postulated that a continuous intrathecal (IT) delivery of low daily doses of riluzole could elevate spinal cord (SC) concentrations well above those achievable with oral treatment alone, without increasing side-effects. METHODS A 6-wk and a 24-wk GLP study were conducted to evaluate the safety of IT riluzole in purpose-bred hound dogs. Oral riluzole, equivalent to 50 mg BID in humans, was administered in combination with one of 3 IT doses given through continuous infusion. Plasma, SC, and brain concentrations of riluzole were measured, along with assessments of safety and tolerability. RESULTS In the 6-wk study, when combining the oral and IT routes, IT infusion significantly increased SC concentrations well above those achieved with oral drug administration alone, without increasing brain concentrations. All IT doses in combination with oral administration were well tolerated by the animals. In the 6-mo study, the lowest dose used in the 6-wk study was dropped and a higher dose was added. This highest dose of IT riluzole was not tolerated by the dogs and yielded SC and brain concentrations significantly higher than achieved in any of our previous studies. CONCLUSION Continuous IT administration of riluzole when combined with oral administration can increase the SC concentration of riluzole above those achievable with oral therapy, without increasing the risk for adverse events associated with systemic drug exposure or off-target side-effects in the brain. Therefore, IT riluzole infusion when used in conjunction with oral therapy may safely enhance lower motor neuron neuroprotection and improve the survival benefit of the drug through enhanced SC delivery, and, with a careful selection of IT doses, it could be implemented in patients with ALS.

Phase I trial of concurrent intraperitoneal and continuous intravenous infusion of fluorouracil in patients with refractory cancer.

1988 ◽  
Vol 6 (1) ◽  
pp. 158-162 ◽  
Author(s):  
B Reichman ◽  
M Markman ◽  
T Hakes ◽  
N Kemeny ◽  
D Kelsen ◽  
...  
Keyword(s):  
Phase I ◽  
Intravenous Infusion ◽  
Phase I Study ◽  
Clinical Utility ◽  
Phase I Trial ◽  
Drug Exposure ◽  
Continuous Intravenous Infusion ◽  
Future Studies ◽  
Systemic Drug Exposure ◽  
Systemic Drug

In an effort to maximize both local-regional and systemic drug exposure to tumor in the peritoneal cavity, a phase I study was conducted that examined the simultaneous daily intraperitoneal (IP) and continuous intravenous infusion (CVI) of fluorouracil (5-FU) to 32 patients with refractory cancer. IP 5-FU administered at 1,000 mg/d with concurrent 5-FU by CVI at 1,000 mg/m2/d for four consecutive days was well tolerated. One patient with a primary gastrointestinal (GI) malignancy with minimal volume disease experienced a surgically defined complete remission. In theory, this regimen may demonstrate clinical utility as an adjuvant treatment of certain GI malignancies. Future studies are planned in this clinical setting.

scholarly journals Oral Lichenoid Reaction: An Uncommon Side Effect of Rituximab

2019 ◽  
Vol 2019 ◽  
pp. 1-3 ◽  
Author(s):  
Amerigo Giudice ◽  
Francesco Liborio ◽  
Fiorella Averta ◽  
Selene Barone ◽  
Leonzio Fortunato
Keyword(s):  
Side Effect ◽  
Oral Lichen Planus ◽  
Drug Exposure ◽  
B Cell Lymphoma ◽  
Systemic Drug Exposure ◽  
Lichenoid Reactions ◽  
The Right ◽  
Oral Lichen ◽  
Histopathological Result ◽  
Systemic Drug

Oral lichenoid reactions (OLR) can be caused by systemic drug exposure. To the best of our knowledge, this is the second report describing a case of OLR induced by rituximab administration in a patient with a diagnosis of non-Hodgkin B-cell lymphoma. After 5 doses of rituximab, a typical pattern of OLP was identified with bilateral and symmetrical lesions on the buccal mucosa and on the right lingual margin. This temporal relationship suggested a probable association between oral lesions and drug therapy. The clinical diagnosis of a rituximab-induced OLR was confirmed by an incisional biopsy reporting a histopathological result of lichenoid mucositis consistent with oral lichen planus. Because of the increasing use of rituximab, it is necessary to know and recognize this uncommon side effect.

Increased doxorubicin levels in hepatic tumors with reduced systemic drug exposure achieved with complete hepatic venous isolation and extracorporeal chemofiltration

1993 ◽  
Vol 33 (3) ◽  
pp. 251-257 ◽  
Author(s):  
Steven A. Curley ◽  
Diana L. Stone ◽  
George M. Fuhrman ◽  
David C. Hohn ◽  
Zahid H. Siddik ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Hepatic Tumors ◽  
Systemic Drug Exposure ◽  
Systemic Drug

scholarly journals Cannabinoids for the treatment of refractory neuropathic pruritus in amyotrophic lateral sclerosis: A case report

2021 ◽  
pp. 026921632110453
Author(s):  
Kelvin Lou ◽  
Shane Murphy ◽  
Clair Talbot
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Side Effects ◽  
Lessons Learned ◽  
Case Presentation ◽  
Course Of Action ◽  
Research Problems ◽  
Neuropathic Pruritus ◽  
Gastrointestinal Side Effects ◽  
Chronic Pruritus ◽  
Lateral Sclerosis

Background: Neuropathic symptoms have a wide variety of manifestations, ranging from pain to pruritus. Neuropathic pruritus is a type of chronic pruritus related to damaged small fibers. Cannabinoids have evidence to manage neuropathic symptoms. We present a case of refractory neuropathic pruritus that was successfully managed with the use of oral cannabinoids. Case presentation: A 60-year-old male with amyotrophic lateral sclerosis with ongoing pruritus despite the use of standard neuropathic therapies. Possible course of action: Sodium channel and N-methyl-D-aspartate receptor antagonists have evidence for neuropathic symptoms but can cause significant gastrointestinal side effects. Prescription cannabinoids such as nabiximol can be cost prohibitive to use in practice. Synthetic tetrahydrocannabinol products are dose limited by psychoactive side effects. Formulation of a plan: A balanced oral cannabinoid from a licensed producer was preferred as it has evidence for neuropathic symptoms and is generally well tolerated. Outcome: The patient showed improvement to his pruritus score from 7/10 to 3/10. There was initial increased sedation but tolerance developed quickly. Lessons learned from case: Cannabinoids are possibly safe and effective in management of neuropathic pruritus. View on research problems: Additional research is needed to establish efficacy and safety.

scholarly journals Symmetrical drug-related intertriginous and flexural exanthema due to clindamycin

2019 ◽  
Vol 12 (8) ◽  
pp. e230077 ◽  
Author(s):  
Virginia Cabrera Hernandez ◽  
Monica Gonzalez Afonso ◽  
Ariel Callero Viera ◽  
Lidon Martin-Fernandez Martin
Keyword(s):  
Drug Exposure ◽  
Systemic Exposure ◽  
Standard Test ◽  
Skin Tests ◽  
Hypersensitivity Response ◽  
Cutaneous Eruption ◽  
Systemic Involvement ◽  
Gold Standard Test ◽  
Systemic Drug Exposure ◽  
Systemic Drug

Systemic drug exposure can produce a skin reaction consisting of symmetrical erythema involving the gluteal and intertriginous areas in the absence of systemic involvement. Symmetrical drug-related intertriginous and flexural exanthema (SDRIFE) occurs after systemic exposure to a drug in which the patient was not previously sensitised, either in the first dose or after several doses. The mechanism of SDRIFE is unknown but is hypothesised to be the result of a delayed hypersensitivity response resulting in a cutaneous eruption some days after the exposure to the drug. The diagnosis should be clinical, based on the history and examination, but skin tests can also be performed to confirm sensitisation. But, as always, the gold-standard test is oral provocation. It is important to know this clinical entity to prevent re-exposure to the responsible allergen in the future.

scholarly journals Amoxicillin-Clavulanic Acid Empirical Oral Therapy for the Management of Children with Acute Haematogenous Osteomyelitis

Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 525
Author(s):  
Elena Serrano ◽  
Irene Ferri ◽  
Luisa Galli ◽  
Elena Chiappini
Keyword(s):  
Clavulanic Acid ◽  
Oral Therapy ◽  
Clinical Laboratory ◽  
Oral Treatment ◽  
Generation Cephalosporin ◽  
Oral Drug ◽  
Oral Antibiotic ◽  
Paediatric Hospital ◽  
Amoxicillin Clavulanic Acid ◽  
Haematogenous Osteomyelitis

According to the Guidelines of the European Society of Pediatric Infectious Diseases (ESPID), in low methicillin-resistant Staphylococcus aureus (MRSA) prevalence settings, short intravenous therapy is recommended in uncomplicated cases of acute haematogenous osteomyelitis (AHOM), followed by empirical oral therapy, preferentially with first/second-generation cephalosporin or dicloxacillin or flucloxacillin. However, several practical issues may arise using some of the first-line antibiotics such as poor palatability or adherence problems. Clinical, laboratory and therapeutic data from children with AHOM hospitalized in one Italian Paediatric Hospital between 2010 and 2019 were retrospectively collected and analyzed. The aim of the study was to highlight the extent of the use and the possible role of amoxicillin-clavulanic acid in the oral treatment of children with AHOM. Two hundred and ten children were included. S.aureus was identified in 42/58 children (72.4% of identified bacteria); 2/42 S.aureus isolates were MRSA (4.8%). No Kingella kingae was identified. Amoxicillin-clavulanic acid was the most commonly used oral drug (60.1%; n = 107/178) and it was associated with clinical cure in all treated children. Overall, four children developed sequelae. One (0.9%) sequela occurred among the 107 children treated with amoxicillin-clavulanic acid. Our results suggest that amoxicillin-clavulanic acid might be an option for oral antibiotic therapy in children with AHOM.

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