Volume 58 (2020), No. 12/2020(December)
The online-version will be updated before the print-version of this Journal is published. Upon request we will send the password and user name by e-mail. The online-service is only available for subscribers of the print-version, if proof of purchase is submitted.
The use of the online-version will be charged with an extra fee (additional to the subscription of the print-version). The service can be used until December 31st of the year of subscription.
|
| Price of the complete print-issue: 35.00$ |
Add to Cart
|
Editorial
COVID-19 and the orphan biologic polyvalent immunoglobulin – “Let food be thy medication” (Hippocrates of Kos c. 460 – c. 370 BC)
Barry G. Woodcock
Page No. 675
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 12/2020 (675-677)
COVID-19 and the orphan biologic polyvalent immunoglobulin – “Let food be thy medication” (Hippocrates of Kos c. 460 – c. 370 BC)
Barry G. Woodcock
Correspondence to:
Barrington (Barry) G. Woodcock
Action Group Immunoglobulins in Anticancer and
Antiinflammation Therapy (AGIGAAT)
POB 200232, 63308 Rödermark, Germany
www.agigaat.com
Email: [email protected]
Position Paper
COVID-19: Cytokine storm modulation/blockade with oral polyvalent immunoglobulins (PVIG, KMP01D): A potential and safe therapeutic agent (Primum nil nocere)
Laura M. Sly, Peter Braun, and Barry G. Woodcock
Price
42.00 $
Page No. 678
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 12/2020 (678-686)
COVID-19: Cytokine storm modulation/blockade with oral polyvalent immunoglobulins (PVIG, KMP01D): A potential and safe therapeutic agent (Primum nil nocere)
Laura M. Sly1, Peter Braun2, and Barry G. Woodcock2
1BC Children’s Hospital Research Institute, Vancouver, BC, Canada, and 2ActionGroup for ImmunoGlobulins in Anticancer/Anti-inflammation Therapy (AGIGAAT), Rödermark, Germany (https://www.agigaat.com)
Although medication treatment in COVID-19 patients would have no direct effect on the spread of the disease, a shortening of the period of hospitalization by only a few days would release 25 – 30% of critical-care resources. However, there appears to be no well-established medication treatment available that can do this reliably at the present time. Anti-malarials currently being evaluated, i.e., chloroquine and hydroxychloroquine, are not yet established as effective medications, and antiviral agents, including remdesivir, are only weakly active. This position paper report is focused on the modulation of the cytokine storm since it appears to be a major cause of the multi-organ failure in COVID-19. Whereas corticosteroids are not recommended in patients not on mechanical ventilation, immunotherapy with convalescent plasma and intravenous immunoglobulin (IVIG) have been used with some success in COVID-19. There is emerging new evidence that polyvalent immunoglobulins (PVIG) from bovine colostrum given orally can also modulate the immune response. Research using lipopolysaccharide-stimulated peripheral blood mononuclear cells from colorectal cancer patients (a so called micro-cytokine storm) has shown that PVIG block the expression of pro-inflammatory cytokines and stimulate the expression of anti-inflammatory cytokines. We have been able to confirm these results in a similar model using mononuclear cells from healthy subjects and could demonstrate that the modulations produced by PVIG are quantitatively and qualitatively similar to those obtained using human immunoglobulin (IVIG). Both immunoglobulins reduce the lipopolysaccharide-induced increase in inflammatory cytokines, interleukin (IL-) 12/23p40 (–90%), IL-6 (–75%) and TNF-α (–60%) and increased the levels of the anti-inflammatory cytokine, IL-10 (+75%). Evidence is presented that PVIG can produce anti-inflammatory effects similar to these after oral application in patients. Its use is contraindicated in patients with lactose intolerance but is otherwise safe and free of complications in clinical studies including the treatment of infants with gastrointestinal disorders.
Conclusion: PVIG appears to be a potential and safe anti-inflammatory agent and can be recommended as a candidate medication for studies in COVID-19 patients.
Correspondence to:
Prof. Barrington (Barry) G. Woodcock
AGIGAAT
PO Box 200232, 63308 Rödermark, Germany
Email: woodcock@
clinpharmacol.com
Original
Domperidone prescribing patterns in pediatric patients before and after safety warning in South Korea
Kiyon Rhew, Nayoung Han, Amie J. Goodin, and Jung Mi Oh
Price
42.00 $
Page No. 687
Abstract
nternational Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 12/2020 (687-695)
Domperidone prescribing patterns in pediatric patients before and after safety warning in South Korea
Kiyon Rhew1#2, Nayoung Han1, Amie J. Goodin3, and Jung Mi Oh1
1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, 2College of Pharmacy, Dongduk Women’s University, Seoul, Republic of Korea, and 3Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL, USA
Objective: In 2014, the Korean Ministry of Food and Drug Safety (MFDS) issued a safety warning to carefully consider adverse cardiac effects when prescribing domperidone for children. We conducted this study to compare the trends of domperidone prescription in pediatrics before and after the MFDS safety warning.
Materials: This study included patients < 18 years old who used national health insurance services within the year 2011 and the year 2016, sampled from Health Insurance Review Agency data.
Methods: We analyzed domperidone prescribing patterns including prescribed daily dosage, maximum period of continuous prescription, and number and types of co-prescribed medications and compared two different years pre and post safety warning.
Results: A total of 16,614 pediatric patients (1.74%) received domperidone prescriptions in 2011, and 11,317 patients (1.23%) in 2016. The probability of receiving at least one prescription in 2016 has been reduced by 30% compared to 2011. Gastritis was the most common indication in both years. The number of prescriptions containing a maximum daily dosage of over 30 mg was significantly lower in 2016. In the same time period, the number of cases with a maximum continuous prescription period of more than 7 days significantly decreased (p < 0.001). In addition, from 2011 to 2016, comorbid diseases of domperidone-treated patients were similar, but the number of co-prescriptions of interacting medication to domperidone decreased (p < 0.001).
Conclusion: After the 2014 safety letter was released, the pattern of prescribing domperidone in pediatrics has enhanced drug safety for children in terms of frequency of prescriptions, maximum duration of domperidone use, and the prescription of drugs interacting with domperidone.Correspondence to:
Jung Mi Oh, PharmD
College of Pharmacy and Research Institute of
Pharmaceutical Sciences
Seoul National University
1 Gwanak-ro, Gwanak-gu, Seoul, 08826, Republic of Korea
Email: [email protected]
Original
Synergistic effect of bevacizumab and celecoxib on angiogenesis in vitro using human umbilical vein endothelial cells
Abdul Qadir, Mohsin Wahid, Mahayrookh Asif, and Talat Roome
Price
42.00 $
Page No. 696
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 12/2020 (696-702)
Synergistic effect of bevacizumab and celecoxib on angiogenesis in vitro using human umbilical vein endothelial cells
Abdul Qadir1#3, Mohsin Wahid1#2, Mahayrookh Asif3, and Talat Roome2
1Dow Research Institute of Biotechnology and Biomedical Sciences, 2Department of Pathology, Dow International Medical College, and 3Department of Pharmacology, Dow International Medical College, Dow University of Health Sciences, Pakistan
Objective: Angiogenesis is the underlying cause of a large number of neoplastic diseases. It is necessary for tumor metastasis, and without it the tumor cannot grow or metastasize. This study aimed to determine the synergistic effect of bevacizumab and celecoxib on angiogenesis using human umbilical vein endothelial cells (HUVEC) as an in vitro model.
Materials and methods: HUVEC were isolated from the umbilical cord by enzymatic digestion using collagenase type IV. HUVEC characterization was done by flow cytometry using cell surface markers CD31, CD105, CD146, and CD45. HUVEC were treated with bevacizumab, celecoxib, and the combination of both drugs and the cell viability was assessed using MTT assay. The formation of capillary-like endotubes for angiogenesis was analyzed using a tube formation assay by measuring the total length of capillary tubes and branch points.
Results: Morphologically, HUVEC showed a typical cobblestone appearance using inverted-phase contrast microscopy and were further evaluated using flow cytometry, which showed positive expression for cell surface markers CD31, CD105, CD146, and negative for CD45. Celecoxib, bevacizumab, and the combination of both drugs showed a dose-dependent inhibition on HUVEC viability. Celecoxib inhibited total tube length by 15% and branch points by 16.5%. Bevacizumab inhibited total tube length by 34% and branch points by 49%. When the two drugs were combined, the total tube length was reduced due to synergism by 68% and branch points by 80%, and the difference was found to be statistically significant (p < 0.001).
Conclusion: Bevacizumab and celecoxib have a synergistic effect in inhibiting in vitro angiogenesis and their combination achieved more strong inhibition than either drug alone.Correspondence to:
Dr. Mohsin Wahid, MBBS, MPhil, PhD
Department of Pathology
Dow International Medical College
Dow University of Health Sciences
Karachi, Pakistan
Email: mohsin.wahid@
duhs.edu.pk
Original
Role of eosinophilic chronic rhinosinusitis in switching to benralizumab treatment in mepolizumab responders
Satoshi Hamada, Yoshiki Kobayashi, and Hirotaka Yasuba
Price
42.00 $
Page No. 703
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 12/2020 (703-708)
Role of eosinophilic chronic rhinosinusitis in switching to benralizumab treatment in mepolizumab responders
Satoshi Hamada1, Yoshiki Kobayashi2, and Hirotaka Yasuba3
1Department of Respiratory Medicine, Hikone Municipal Hospital, Shiga, 2Department of Otolaryngology, Kansai Medical University, Osaka, and 3Department of Airway Medicine, Mitsubishi Kyoto Hospital, Kyoto, Japan
Background: There are currently three anti-interleukin-5 (IL-5) pathway-directed therapies: mepolizumab, reslizumab, and benralizumab. Of these, benralizumab was most recently approved. Benralizumab is administered every 8 weeks after an initial 3 doses given every 4 weeks, whereas mepolizumab and reslizumab are administered every 4 weeks. This convenience in benralizumab administration indicates that it is potentially beneficial for patients. Therefore, we potentially have an opportunity to change to benralizumab in patients who responded to mepolizumab or reslizumab. However, other than eosinophil levels, factors that could predict patients responding to anti-IL-5 pathway-directed therapies have been unknown. In this study, we examine the clinical characteristics of mepolizumab responders who achieved successful switching to benralizumab. Materials and methods: A total of 18 consecutive severe asthmatic patients treated with sequential mepolizumab and benralizumab, each for at least 1 year, were enrolled in this study. This study was a single-center case series. Patients were defined as having achieved successful switching to benralizumab if they satisfied either of the following for 1 year before and after the benralizumab treatment: (1) they experienced no exacerbation; or (2) they experienced no exacerbation and discontinued oral corticosteroids. Results: All 18 patients responded to mepolizumab treatment, and 11 of them achieved successful switching to benralizumab. The proportion of patients who achieved successful switching to benralizumab was higher in patients with eosinophilic chronic rhinosinusitis (ECRS) than in those without (76.9 vs. 20.0%; p = 0.025). Conclusion: Our findings imply that in responders to mepolizumab, there may be a higher response rate to benralizumab in patients with ECRS than in those without.
Correspondence to:
Satoshi Hamada, MD, PhD
Department of Respiratory Medicine
Hikone Municipal Hospital
1882 Hassakacho, Shiga, 522-8539, Japan
Email: sh1124@
kuhp.kyoto-u.ac.jp
Original
New index of abdominal obesity, a body shape index, is BMI-independently associated with systemic arterial stiffness in real-world Japanese population
Daiji Nagayama, Yasuhiro Watanabe, Takashi Yamaguchi, Mitsuya Maruyama, Atsuhito Saiki, Kohji Shirai, and Ichiro Tatsuno
Price
42.00 $
Page No. 709
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 12/2020 (709-717)
New index of abdominal obesity, a body shape index, is BMI-independently associated with systemic arterial stiffness in real-world Japanese population
Daiji Nagayama1, Yasuhiro Watanabe2, Takashi Yamaguchi2, Mitsuya Maruyama3, Atsuhito Saiki2, Kohji Shirai4, and Ichiro Tatsuno2
1Department of Internal Medicine, Nagayama Clinic, Tochigi, 2Center of Diabetes, Endocrinology and Metabolism, Toho University, Sakura Medical Center, Chiba, 3Fukuda Denshi Co., Ltd., Tokyo, and 4Department of Internal Medicine, Mihama Hospital, Chiba, Japan
Objective: To clarify that the new index of abdominal obesity, a body shape index (ABSI), is associated with obesity-related metabolic disorders and arterial stiffness.
Materials: We analyzed the cross-sectional data from 62,514 Japanese subjects (mean age 44.4 years, mean body mass index (BMI) 22.2 kg/m2) without a past history of cardiovascular disease, stroke, or treatment for obesity-related metabolic disorders.
Methods: Various body adiposity indices including BMI, waist circumference (WC), and ABSI were evaluated for abilities to indicate metabolic disorders and arterial stiffness assessed by cardio-ankle vascular index (CAVI).
Results: WC, WC/height ratio, and WC/BMI ratio correlated with BMI regardless of gender or obesity, whereas ABSI hardly correlated with BMI. ROC analyses demonstrated that ABSI had the highest discriminatory power in predicting high CAVI (≥ 90th percentile) compared to other body adiposity indices, and the cut-off value was 0.080. Increases in ABSI as well as BMI reflected severity of metabolic disorders. After adjusting for confounders identified by multiple regression analysis, adjusted CAVI correlated positively with ABSI, whereas an inverted relationship was observed between adjusted CAVI and BMI. Additionally, the contribution of high ABSI (≥ 0.080) for high CAVI was independent of gender, age, obesity, and obesity-related metabolic disorders in the multivariate logistic regression model.
Conclusion: ABSI is an easily calculated index of abdominal obesity which reflects metabolic disorders and systemic arterial stiffening, and may be useful in primary health screening even without any medical equipment for visceral fat quantification.Correspondence to:
Daiji Nagayama, MD, PhD
Nagayama Clinic
2-12-22, Tenjin-Cho, Oyama-City
Tochigi, 323-0032, Japan
Email: deverlast96071@
gmail.com
Original
Evaluation of injectable metamizole utilization in children and adults in primary care
Caner Vizdiklar, Narin Akici, Volkan Aydin, Basak Donertas, Ali Alkan, and Ahmet Akici
Price
42.00 $
Page No. 718
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 12/2020 (718-726)
Evaluation of injectable metamizole utilization in children and adults in primary care
Caner Vizdiklar1, Narin Akici2, Volkan Aydin1, Basak Donertas3, Ali Alkan4, and Ahmet Akici1
1Department of Medical Pharmacology, School of Medicine, Marmara University, 2Department of Pediatrics, Haydarpasa Numune Training and Research Hospital, Istanbul, 3Department of Medical Pharmacology, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, and 4Turkish Medicines and Medical Devices Agency, Ministry of Health, Ankara, Turkey
Objective: Use of injectable metamizole in the outpatient setting is controversial due to safety concerns. We aimed to compare injectable metamizole prescribing patterns for children and adults with further evaluation of nationwide metamizole consumption trend.
Materials and methods: In this retrospective cross-sectional study, 100 injectable drug-containing prescriptions written in each month of 2010 in 32 provinces of Turkey were selected. Drug utilization patterns on injectable metamizole-containing prescriptions (n = 1,270) were analyzed and compared by “pediatric” and “adult” groups. Additionally, nationwide outpatient consumption data from 2010 to 2018 were obtained, and the utilization trend was examined.
Results: Children received 12.4% of injectable metamizole-containing prescriptions. Male predominance was observed in children (62.7%), as opposed to female predominance in adults (55.2%, p < 0.05). The most frequent diagnoses were “acute tonsillopharyngitis” and “acute bronchitis” in both groups. Single-diagnosis prescriptions constituted 79.1% of the pediatric group and 53.1% of the adult group (p < 0.05). Diagnoses, drugs, and injectable analgesics per prescription were significantly higher in adults (1.68 ± 0.86, 3.45 ± 0.90, and 1.06 ± 0.23, respectively) than in children (1.22 ± 0.43, 3.25 ± 0.88, and 1.00, respectively) (p < 0.05). The percentage of prescriptions containing injectable antibiotics was higher in children (83.6%) than in adults (64.9%). Outpatient injectable metamizole consumption showed a decreasing trend in 2010 – 2018.
Conclusion: Despite recent downward trend, prescribing of injectable metamizole in primary care was considerably prevalent. This study, which highlights fundamental differences among metamizole utilization patterns in children and adults, addresses the inadequacy of rational use of the drug in terms of preferred indications and accompanying drugs.Correspondence to:
Prof. Ahmet Akici, MD
Department of Medical Pharmacology
Marmara University School of Medicine
Basibuyuk Road 9/2
34854, Maltepe, Istanbul, Turkey
Email: [email protected]
Case
Report
Hyperammonemia with impaired consciousness caused by continuous 5-fluorouracil infusion for colorectal cancer: A case report
Toshiki Nakamura, Soichi Shibata, Yusuke Miyatani, and Hajime Matsubara
Price
42.00 $
Page No. 727
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 12/2020 (727-731)
Hyperammonemia with impaired consciousness caused by continuous 5-fluorouracil infusion for colorectal cancer: A case report
Toshiki Nakamura1, Soichi Shibata1, Yusuke Miyatani2, and Hajime Matsubara1#3
1Department of Pharmacy, 2Department of Gastroenterology, Kitasato Institute Hospital, and 3Division of Clinical Pharmacy (Laboratory of Pharmacy Practice and Science III) and Research and Education Center for Clinical Pharmacy, School of Pharmacy, Kitasato University, Tokyo, Japan
A 66-year-old woman was diagnosed with stage IVb sigmoid colon cancer. Modified FOLFOX-6 (mFOLFOX-6; levofolinate‒fluorouracil‒oxaliplatin) plus panitumumab was selected as the chemotherapeutic regimen, but she was administered a regimen without oxaliplatin (L-OHP) or bolus 5-fluorouracil (5-FU) because of her general condition and concern about adverse effects. The patient had impaired consciousness on day 3 of chemotherapy. Computed tomography (CT) and magnetic resonance imaging (MRI) of the brain showed no findings of hemorrhage, infarction, brain metastasis, and leukoencephalopathy. Except for high blood ammonia concentration (353 µg/dL), there were no other findings that could have caused her condition. Impaired consciousness due to hyperammonemia was diagnosed. We started an intravenous drip supplemented with branched chain amino acids for liver protection. Approximately 6 hours later, blood ammonia level improved to 88 µg/dL, which approached the reference value. Consciousness level improved over time, reaching a level of alertness on day 5 after starting chemotherapy. 5-FU was suspected to be the cause of impaired consciousness due to hyperammonemia, but the exact cause could not be identified because most of the previously reported cases were given L-OHP, bolus 5-FU, and other concomitant medications. In this case, since there were no other concomitant medications, it is highly probable that continuous infusion of 5-FU alone caused impaired consciousness due to hyperammonemia. This is an important case that indicates the need to monitor carefully for the occurrence of hyperammonemia when 5-FU is administered continuously; it also proposes future issues for investigation.Correspondence to:
Toshiki Nakamura, MSc
Department of
Pharmacy, Kitasato Institute Hospital
5-9-1 Shirokane,
Minato-ku, Tokyo 108-8642, Japan
Email:
toshi-n@
insti.kitasato-u.ac.jp
Case
Report
Necrotizing leukocytoclastic small vessel vasculitis associated with letrozole: A case report
Fatemeh Mohaghegh and Bahareh Bahrami
Price
42.00 $
Page No. 732
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 12/2020 (732-735)
Necrotizing leukocytoclastic small vessel vasculitis associated with letrozole: A case report
Fatemeh Mohaghegh and Bahareh Bahrami
Department of Dermatology, Isfahan University of Medical Science, Isfahan, Iran
Introduction: Letrozole is an aromatase inhibitor that used to treat breast cancers. Letrozole-associated skin vasculitis is a rare side effect of this medication, in this study we report a case of necrotizing type of Small vessel cutaneous vasculitis associated with letrozole consumption.
Case presentation: A 45-year-old woman was referred to the dermatology clinic with painful necrotic annular lesions on the lower limbs. Her past medical history showed evidence of breast cancer and taking letrozole. Five months after the start of letrozole, the patient’s signs and symptoms had appeared. Physical examination revealed annular plaques with erythematous margin and multiple necrotic centers that were painful to touch. The histopathology showed extravasated red blood cells and leukocytoclasis as well as neutrophils surrounding and infiltrating the wall of blood vessels in superficial and mid dermis. We discontinued letrozole, then prescribed topical clobetasol, systemic prednisolone, and colchicine; the lesions began to heal after 1 month from the start of treatment, and did not recur after discontinuing the treatment.
Discussion: Pathogenesis of vasculitis caused by aromatase inhibitors is not fully elucidated, but estrogen depletion and idiosyncratic drug reaction has been proposed. Cutaneous leukocytoclastic small vessel vasculitis (CLSVV) resulting from aromatase inhibitors is relatively rare so it is recommended to consider drug-induced CLSVV in other patients treated with aromatase inhibitors.Correspondence to:
Dr. Bahareh Bahrami
Department of Dermatology
Isfahan University of Medical Science
Hezar Jerib Street, 81746-73461 Isfahan, Iran
Email: [email protected]
Case
Report
Lacosamide-induced recurrent ventricular fibrillation: A case report
Georgios Eleftheriou, Raffaella Butera, Mariapina Gallo, Andrea Giampreti, Lorella Faraoni, Maria Gioia Contessa, and Giuseppe Bacis
Price
42.00 $
Page No. 736
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 12/2020 (736-739)
Lacosamide-induced recurrent ventricular fibrillation: A case report
Georgios Eleftheriou, Raffaella Butera, Mariapina Gallo, Andrea Giampreti, Lorella Faraoni, Maria Gioia Contessa, and Giuseppe Bacis
Poison Control Center, ASST Papa Giovanni XXIII, Bergamo, Italy
Lacosamide, a new antiepileptic drug, acts at central nervous system level but may also affect the heart, increasing the risk of cardiac arrhythmias. Only few cases of lacosamide-induced cardiac dysrhythmia have been published. We report a case of several episodes of a life-threatening ventricular fibrillation requiring cardioversion following the first doses of lacosamide as adjunctive epilepsy treatment.Correspondence to:
Georgios Eleftheriou, MD, PhD, MSc
Poison Control Center
Piazza OMS, 1, ASST Papa Giovanni XXIII
24128 Bergamo, Italy
Email: geleftheriou@
asst-pg23.it
Case
Report
Rituximab may cause higher mortality in young autoimmune disease patients with rituximab-induced interstitial lung disease: A case report and systematic review of the literature
Zhanwen He, Ruohao Wu, Ping Bai, and Kunyin Qiu
Price
42.00 $
Page No. 740
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 12/2020 (740-748)
Rituximab may cause higher mortality in young autoimmune disease patients with rituximab-induced interstitial lung disease: A case report and systematic review of the literature
Zhanwen He1#2*, Ruohao Wu1#2*, Ping Bai2#3, and Kunyin Qiu1#2
1Department of Children’s Neuro-endocrinology, Sun Yat-sen Memorial Hospital, 2Key Laboratory of Malignant Tumor Gene Regulation and Target Therapy of Guangdong High Education Institutes, and 3General Department, Sun Yat-sen Memorial Hospital, Sun Yat-sen University Guangzhou, Guangzhou, China
Background: MOG-IgG-associated encephalomyelitis (MOG-EM), a of common type of autoimmune encephalomyelitis (AE), is an autoimmune disease (AID) of the central nervous system that predominantly affects the brain and spinal cord. Rituximab (RTX) – a chimeric anti-CD20 monoclonal antibody – has been increasingly used as an effective immunotherapeutic agent in the treatment of AE. However, interstitial lung disease (ILD) is an exceedingly rare but potentially fatal complication of RTX treatment.
Case report and review of the literature: Herein, we describe the first case of RTX-induced ILD (R-ILD) in a teenager with MOG-EM. In addition, we systematically review the literature on R-ILD cases in patients with AID and discuss the clinical characteristics of R-ILD in individuals with differential diagnosis of AID.
Conclusion: R-ILD should be suspected in patients with AE undergoing RTX treatment who present with dyspnea and/or cough without any signs or symptoms of infection. Meanwhile, by reviewing the literature systematically, we suggest that regardless of the dosage, RTX therapy for AID should be very cautious and well-monitored especially in young individuals including age groups of children, adolescents, and young adults due to the possibility of relatively higher mortality caused by R-ILD.
*Equal contributors.Correspondence to:
Prof. Zhanwen He
Department of Children’s Neuro-endocrinology
Sun Yat-sen memorial hospital
Sun Yat-sen university
33 Yingfeng Road
Guangzhou, Guangdong 510120, P.R. China
Email: hezhanw@
mail.sysu.edu.cn
Bioavailability Section
A randomized, open-label, crossover study to compare the safety and pharmacokinetics of two tablet formulations of tenofovir (tenofovir disoproxil and tenofovir disoproxil fumarate) in healthy subjects
Jae Nam Yun, Ji-Sun Yeun, Hye-Su Kan, Minyu Lee, Namsick Kim, Tae-Young Oh, Seung-Kwan Nam, Yoon Seok Choi, In Sun Kwon, Kwang Lae Hoe, and Jang Hee Hong
Price
42.00 $
Page No. 749
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 12/2020 (749-756)
A randomized, open-label, crossover study to compare the safety and pharmacokinetics of two tablet formulations of tenofovir (tenofovir disoproxil and tenofovir disoproxil fumarate) in healthy subjects
Jae Nam Yun1, Ji-Sun Yeun4, Hye-Su Kan6, Minyu Lee2, Namsick Kim2, Tae-Young Oh2, Seung-Kwan Nam2, Yoon Seok Choi2, In Sun Kwon4, Kwang Lae Hoe1, and Jang Hee Hong3#4#5
1Department of New Drug Development, Chungnam National University, Daejeon, 2Huons Co., Ltd., Gyeonggi-do, 3Department of Medical Science, College of Medicine, 4Clinical Trials Center, Chungnam National University Hospital, 5Department of Pharmacology, College of Medicine, Chungnam National University College of Medicine and Hospital, Daejeon, and 6Center for Infectious Diseases Control, Korea Centers for Disease Control and Prevention, Cheongju, Republic of Korea
Purpose: This study was performed to compare the pharmacokinetic properties and assess bioequivalence for the test formulation (HUG116 tablet; tenofovir disoproxil) and reference formulation (Viread tablet; tenofovir disoproxil fumarate).
Materials and methods: A randomized, open-label, single-dosing, two-treatment, two-period, two-sequence cross-over study was conducted in 50 healthy subjects. All subjects were randomly assigned to one of the two sequences, and they received a single dose of test or reference formulation in the first period and the alternative formulation during the next period under fasting conditions. Serial blood samples for pharmacokinetic evaluation were collected up to 72 hours post dose, and the pharmacokinetic parameters were estimated by noncompartmental methods. Throughout the study, tolerability was assessed based on adverse events, vital signs, and clinical laboratory tests.
Results: The test formulation showed similar pharmacokinetic profiles to those of the reference formulation. The geometric mean ratio and 90% confidence interval (CI) of the test formulation to the reference formulation for maximum plasma concentration (Cmax) was 0.93 (0.87 – 0.99), and the corresponding value for the area under the concentration-time curve from time zero to time of last quantifiable concentration (AUCt) was 0.94 (0.89 – 0.99). Both CIs were within the conventional bioequivalence range of 0.8 – 1.25. The tolerability profile was not significantly different between the test and reference formulations.
Conclusion: This study found that the PKs of the test formulation (HUG116 tablet; tenofovir disoproxil) and reference formulation (Viread tablet; tenofovir disoproxil fumarate) were similar, and the test formulation met the regulatory criteria for assuming bioequivalence with the reference formulation.Correspondence to:
Jang Hee Hong, MD, PhD
Department of Pharmacology, College of Medicine
Chungnam National University
(Clinical Trials Center, Chungnam National University Hospital)
266 Munhwa-ro, Jung-gu
Daejeon 35015, Republic of Korea
Email: [email protected]
Bioavailability Section
Bioequivalence of perampanel fine granules and tablets in healthy Japanese subjects
Sari Shiba, Hisakuni Sekino, Kaeko Ishiba, Sanae Yasuda, Syuhei Inoue, Ken Kotaka, Larisa Reyderman, and Naoki Uchida
Page No. 757
Abstract
International Journal of Clinical Pharmacology and Therapeutics, Vol. 58 – No. 12/2020 (757-764)
Bioequivalence of perampanel fine granules and tablets in healthy Japanese subjects
Sari Shiba1, Hisakuni Sekino2, Kaeko Ishiba1, Sanae Yasuda1, Syuhei Inoue1, Ken Kotaka1, Larisa Reyderman3, and Naoki Uchida4
1Eisai Co., Ltd., Tokyo, Japan, 2Medical Corporation HOUEIKAI, Sekino Clinical Pharmacology Clinic, Tokyo, Japan, 3Eisai Inc., Woodcliff Lake, NJ, USA, 4School of Medicine, Showa University, Tokyo, Japan
Objective: Perampanel is an approved anti-seizure drug. A new formulation of perampanel fine granules (FG; 1% perampanel) has been developed for patients who are unable to take tablets. Bioequivalence between the 4-mg FG and tablet perampanel formulations, as well as their safety and tolerability, were assessed.
Materials and methods: In this phase I, single-center, open-label, 2-period, 2-sequence, crossover, bioequivalence study (NCT03399734), healthy Japanese subjects were randomized to receive single doses of the 4-mg FG perampanel and 4-mg perampanel tablet (separated by a ≥ 6-week washout period). Plasma samples for perampanel concentration analysis were collected pre-dose and at intervals up to 168 hours post-dose. The maximum observed concentration (Cmax) and area under the concentration–time curve from time zero to 168 hours (AUC(0–168h)) were used to assess the bioequivalence of the two formulations.
Results: The 90% confidence intervals (CIs) for the geometric mean ratio of test/reference for Cmax and AUC(0–168h) were within the bioequivalence criteria of 80 – 125% (Cmax 90% CI 90.8%, 110%; AUC<sub>(0–168h)</sub> 90% CI 98.2%, 112%; N = 21). 10/24 (41.7%) subjects with FG experienced ≥ 1 treatment-emergent adverse event (TEAE). The events were mild in severity and resolved within 4 hours of onset. There were no deaths, severe TEAEs, serious AEs, or TEAEs leading to study-drug withdrawal.
Conclusion: Bioequivalence of 4-mg FG and 4-mg tablet of perampanel was demonstrated. Both perampanel formulations were generally safe and well tolerated. These data suggest that perampanel FG may be a suitable alternative formulation for patients with epilepsy who have difficulties taking perampanel tablets.
Correspondence to:
Sari Shiba, MS
Department of Clinical Pharmacology Science
Eisai Co., Ltd.
4-6-10 Koishikawa, Bunkyo-ku, Tokyo 112-8088, Japan
Email: [email protected]
