scholarly journals Warfarin-Rifampin Drug Interaction in a Pediatric Patient

2017 ◽  
Vol 22 (5) ◽  
pp. 375-377 ◽  
Author(s):  
Michael Poon ◽  
Brady S. Moffett ◽  
Donald L. Yee
Keyword(s):  
Drug Interaction ◽  
Pediatric Patient ◽  
Warfarin Therapy ◽  
Pediatric Patients ◽  
Extreme Case ◽  
Inhibitory Effect ◽  
Adult Patients

Rifampin has been documented to significantly attenuate the effect of warfarin in adult patients. No data have been presented on the use of rifampin and warfarin in a pediatric patient. We report an extreme case of increased warfarin metabolism in a pediatric patient who was concomitantly receiving rifampin, despite receiving other medications that significantly decrease warfarin metabolism. The inhibitory effect of rifampin on warfarin therapy may be amplified in pediatric patients.

Pseudo-Parkinson Disease Secondary to Ritonavir–Buspirone Interaction

2003 ◽  
Vol 37 (2) ◽  
pp. 202-205 ◽  
Author(s):  
Patrick G Clay ◽  
Molly M Adams
Keyword(s):  
Drug Interaction ◽  
Inhibitory Effect ◽  
Hiv Positive ◽  
High Dose ◽  
Resting Tremor ◽  
Case Summary ◽  
History Of ◽  
Drug Drug Interaction ◽  
To Receive

OBJECTIVE: To report a case of Parkinson-like symptoms appearing in a patient after introduction of ritonavir to buspirone therapy. CASE SUMMARY: A 54-year-old HIV-positive white man presented to the clinic with a 2-week history of ataxia, shuffling gait, cogwheel rigidity, resting tremor, and sad affect with masked features. This patient had been receiving high-dose buspirone (40 mg every morning and 30 mg every evening) for 2 years prior to the introduction of ritonavir/indinavir combination therapy (400 mg/400 mg twice daily) 6 weeks prior to initiation of the above symptoms. Buspirone was decreased to 15 mg 3 times daily, ritonavir/indinavir was discontinued, and amprenavir 1200 mg twice daily was added. The patient's symptoms began to subside after 1 week, with complete resolution after about 2 weeks. The patient continued to receive buspirone for an additional 12 months without recurrence of symptoms. DISCUSSION: This is the first reported interaction of buspirone and antiretrovirals. Buspirone, extensively metabolized by CYP3A4, was likely at supratherapeutic levels due to the inhibitory effect of ritonavir and, secondarily, indinavir. The Parkinson-like symptoms developed rapidly and severely, impacted this patient's quality of life, and necessitated significant clinic expenditures to identify this drug–drug interaction. CONCLUSIONS: This case demonstrates a severe drug–drug interaction between buspirone and ritonavir and further demonstrates the need for awareness of the metabolic profile for all agents an HIV-infected patient is receiving.

scholarly journals Macrophage Activation Syndrome in Adults: A Retrospective Case Series

2021 ◽  
Vol 9 ◽  
pp. 232470962110264
Author(s):  
Taylor Warmoth ◽  
Malvika Ramesh ◽  
Kenneth Iwuji ◽  
John S. Pixley
Keyword(s):  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Pediatric Patients ◽  
Inflammatory Diseases ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Case Series ◽  
Adult Patients ◽  
Retrospective Case ◽  
Life Threatening ◽  
Activation Syndrome

Macrophage activation syndrome (MAS) is a form of hemophagocytic lymphohistocytosis that occurs in patients with a variety of inflammatory rheumatologic conditions. Traditionally, it is noted in pediatric patients with systemic juvenile idiopathic arthritis and systemic lupus erythematous. It is a rapidly progressive and life-threatening syndrome of excess immune activation with an estimated mortality rate of 40% in children. It has become clear recently that MAS occurs in adult patients with underlying rheumatic inflammatory diseases. In this article, we describe 6 adult patients with likely underlying MAS. This case series will outline factors related to diagnosis, pathophysiology, and review present therapeutic strategies.

scholarly journals Involvement of Irisin in age-related osteoporosis: positive correlation with BMD in older adult patients and inhibitory effect on the senescent marker p21 in osteoblasts

Bone Reports ◽  
2021 ◽  
Vol 14 ◽  
pp. 100833
Author(s):  
Graziana Colaianni ◽  
Lorenzo Sanesi ◽  
Giuseppina Storlino ◽  
Roberta Zerlotin ◽  
Patrizia Pignataro ◽  
...  
Keyword(s):  
Older Adult ◽  
Inhibitory Effect ◽  
Adult Patients ◽  
Positive Correlation ◽  
Age Related

scholarly journals Risk Factors for Failure After Anterior Cruciate Ligament Reconstruction in a Pediatric Population: A Prediction Algorithm

2021 ◽  
Vol 9 (3) ◽  
pp. 232596712199116
Author(s):  
Nicholas J. Lemme ◽  
Daniel S. Yang ◽  
Brooke Barrow ◽  
Ryan O’Donnell ◽  
Alan H. Daniels ◽  
...  
Keyword(s):  
Risk Factors ◽  
Anterior Cruciate Ligament ◽  
Anterior Cruciate Ligament Reconstruction ◽  
Ligament Reconstruction ◽  
Pediatric Patients ◽  
Cruciate Ligament ◽  
Adult Patients ◽  
Collateral Ligament ◽  
Cruciate Ligament Reconstruction ◽  
Anterior Cruciate

Background: Anterior cruciate ligament reconstruction (ACLR) in pediatric patients is becoming increasingly common. There is growing yet limited literature on the risk factors for revision in this demographic. Purpose: To (1) determine the rate of pediatric revision ACLR in a nationally representative sample, (2) ascertain the associated patient- and injury-specific risk factors for revision ACLR, and (3) examine the differences in the rate and risks of revision ACLR between pediatric and adult patients. Study Design: Case-control study; Level of evidence, 3. Methods: The PearlDiver patient record database was used to identify adult patients (age ≥20 years) and pediatric patients (age <20 years) who underwent primary ACLR between 2010 and 2015. At 5 years postoperatively, the risk of revision ACLR was compared between the adult and pediatric groups. ACLR to the contralateral side was also compared. Multivariate logistic regression was used to determine the significant risk factors for revision ACLR and the overall reoperation rates in pediatric and adult patients; from these risk factors, an algorithm was developed to predict the risk of revision ACLR in pediatric patients. Results: Included were 2055 pediatric patients, 1778 adult patients aged 20 to 29 years, and 1646 adult patients aged 30 to 39 years who underwent ACLR. At 5 years postoperatively, pediatric patients faced a higher risk of revision surgery when compared with adults (18.0 % vs 9.2% [adults 20-29 years] and 7.1% [adults 30-39 years]; P < .0001), with significantly decreased survivorship of the index ACLR ( P < .0001; log-rank test). Pediatric patients were also at higher risk of undergoing contralateral ACLR as compared with adults (5.8% vs 1.6% [adults 20-29 years] and 1.9% [adults 30-39 years]; P < .0001). Among the pediatric cohort, boys (odds ratio [OR], 0.78; 95% CI, 0.63-0.96; P = .0204) and patients >14 years old (OR, 0.62; 95% CI, 0.45-0.86; P = .0035) had a decreased risk of overall reoperation; patients undergoing concurrent meniscal repair (OR, 1.84; 95% CI, 1.43-2.38; P < .0001) or meniscectomy (OR, 2.20; 95% CI, 1.72-2.82; P < .0001) had an increased risk of revision surgery. According to the risk algorithm, the highest probability for revision ACLR was in girls <15 years old with concomitant meniscal and medial collateral ligament injury (36% risk of revision). Conclusion: As compared with adults, pediatric patients had an increased likelihood of revision ACLR, contralateral ACLR, and meniscal reoperation within 5 years of an index ACLR. Families of pediatric patients—especially female patients, younger patients, and those with concomitant medial collateral ligament and meniscal injuries—should be counseled on such risks.

scholarly journals In vitro study on the effect of cornin on the activity of cytochrome P450 enzymes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qun Zhang ◽  
Zengqiang Qu ◽  
Yanqing Zhou ◽  
Jin Zhou ◽  
Junwei Yang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interaction ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Drug Drug Interaction ◽  
Dose Dependent

Abstract Background Cornin is a commonly used herb in cardiology for its cardioprotective effect. The effect of herbs on the activity of cytochrome P450 enzymes (CYP450s) can induce adverse drug-drug interaction even treatment failure. Therefore, it is necessary to investigate the effect of cornin on the activity of CYP450s, which can provide more guidance for the clinical application of cornin. Methods Cornin (100 μM) was incubated with eight isoforms of CYP450s, including CYP1A2, 2A6, 3A4, 2C8, 2C9, 2C19, 2D6, and 2E1, in pooled human liver microsomes. The inhibition model and corresponding parameters were also investigated. Results Cornin exerted significant inhibitory effect on the activity of CYP3A4, 2C9, and 2E1 in a dose-dependent manner with the IC50 values of 9.20, 22.91, and 14.28 μM, respectively (p < 0.05). Cornin inhibited the activity of CYP3A4 non-competitively with the Ki value of 4.69 μM, while the inhibition of CYP2C9 and 2E1 by cornin was competitive with the Ki value of 11.31 and 6.54 μM, respectively. Additionally, the inhibition of CYP3A4 by cornin was found to be time-dependent with the KI/Kinact value of 6.40/0.055 min− 1·μM− 1. Conclusions The inhibitory effect of cornin on the activity of CYP3A4, 2C9, and 2E1 indicated the potential drug-drug interaction between cornin and drugs metabolized by these CYP450s, which needs further investigation and validation.

scholarly journals Interpreting Anion Gap Values in Adult and Pediatric Patients: Examining the Reference Interval

2019 ◽  
Vol 5 (1) ◽  
pp. 126-135
Author(s):  
Nadia Ayala-Lopez ◽  
Roa Harb
Keyword(s):  
Emergency Department ◽  
Intensive Care ◽  
Pediatric Patients ◽  
Reference Interval ◽  
Adult Patients ◽  
Anion Gap ◽  
Moderate Degree ◽  
New Haven ◽  
Repeated Testing ◽  
Median Percent Change

Abstract Background The anion gap is primarily used in the diagnosis of acid-base disorders. We conducted a study to determine the anion gap reference interval in our patient population, investigated the workup of abnormal vs normal anion gaps, and examined the anion gap variation upon repeated testing. Methods A retrospective review was performed on 17137 adult and pediatric patients who presented to Yale-New Haven Hospital outpatient clinics, emergency department, or intensive care units between 2012 and 2017. Results We derived a new reference interval of 7 to 18 mmol/L with a median of 13 mmol/L in healthy adults with no significant differences owing to partitioning by sex or age. Based on the new reference interval, 5%, 23%, and 18% of healthy, emergency department, and intensive care unit adult patients, respectively, were misclassified as having high values with the previous interval of 6 to 16 mmol/L. However, there were no significant differences in the number of tests ordered in patients with anion gaps above and below the upper limit of the previous reference interval. The majority of increased anion gaps that were repeated normalized by 12 h. In a subgroup of healthy adult patients with annual testing, the median percent change in each patient's anion gap from 2015 to 2016 was approximately 13%. Conclusions The anion gap should be used with an appropriate reference interval to avoid misclassification. There may be a moderate degree of individuality that argues for comparing the anion gap with its baseline value in the same patient pending further studies that formally derive its biological variation.

scholarly journals Voriconazole Pharmacokinetics and Safety in Immunocompromised Children Compared to Adult Patients

2010 ◽  
Vol 54 (8) ◽  
pp. 3225-3232 ◽  
Author(s):  
Claudia Michael ◽  
Uta Bierbach ◽  
Katrin Frenzel ◽  
Thoralf Lange ◽  
Nadezda Basara ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Fungal Infections ◽  
Adult Patients ◽  
European Medicines Agency ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Entire Study ◽  
Interindividual Variations ◽  
Concentration Time ◽  
Days Of Therapy

ABSTRACT The aim of this study was to investigate the pharmacokinetics and safety of voriconazole after intravenous (i.v.) administration in immunocompromised children (2 to 11 years old) and adults (20 to 60 years old) who required treatment for the prevention or therapy of systemic fungal infections. Nine pediatric patients were treated with a dose of 7 mg/kg i.v. every 12 h for a period of 10 days. Three children and 12 adults received two loading doses of 6 mg/kg i.v. every 12 h, followed by a maintenance dose of 5 mg/kg (children) or 4 mg/kg (adults) twice a day during the entire study period. Trough voriconazole levels in blood over 10 days of therapy and regular voriconazole levels in blood for up to 12 h postdose on day 3 were examined. Wide intra- and interindividual variations in plasma voriconazole levels were noted in each dose group and were most pronounced in the children receiving the 7-mg/kg dose. Five (56%) of them frequently had trough voriconazole levels in plasma below 1 μg/ml or above 6 μg/ml. The recommended dose of 7 mg/kg i.v. in children provides exposure (area under the concentration-time curve) comparable to that observed in adults receiving 4 mg/kg i.v. The children had significantly higher C max values; other pharmacokinetic parameters were not significantly different from those of adults. Voriconazole exhibits nonlinear pharmacokinetics in the majority of children. Voriconazole therapy was safe and well tolerated in pediatric and adult patients. The European Medicines Agency-approved i.v. dose of 7 mg/kg can be recommended for children aged 2 to <12 years.

Extensive Extraneural Metastases of Cerebral Glioblastoma in a Pediatric Patient: An Extreme Case Report and Comprehensive Review of the Literature

2021 ◽  
pp. 1-6
Author(s):  
Kadir Oktay ◽  
Dogu Cihan Yildirim ◽  
Arbil Acikalin ◽  
Kerem Mazhar Ozsoy ◽  
Nuri Eralp Cetinalp ◽  
...  
Keyword(s):  
Case Report ◽  
Pediatric Patients ◽  
Extreme Case ◽  
Rare Condition ◽  
Review Of The Literature ◽  
Pertinent Literature ◽  
Cervical Lymph Nodes ◽  
Case Presentation ◽  
Comprehensive Review ◽  
Extraneural Metastases

<b><i>Introduction:</i></b> Extraneural metastases of glioblastoma are very rare clinical entities, especially in pediatric patients. Because of their rarity, they can be confused with other pathological processes. <b><i>Case Presentation:</i></b> We report a case of 16-year-old boy with extensive extraneural metastases of glioblastoma. Lung, liver, cervical lymph nodes, skin, and bone metastases were detected in the patient. <b><i>Conclusion:</i></b> We describe the presentation, evaluation, and diagnosis of this rare condition with regard to pertinent literature.

Increased Plasma YKL-40 Level and Chitotriosidase Activity in Cystic Fibrosis Patients

2021 ◽  
Author(s):  
Dilara Bal Topcu ◽  
Gökcen Tugcu ◽  
Berrin Er ◽  
Sanem Eryilmaz Polat ◽  
Mina Hizal ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pediatric Patients ◽  
Adult Patients ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Children ◽  
Plasma Samples ◽  
Stable Period ◽  
Valuable Marker ◽  
Chitotriosidase Activity ◽  
Relevant Factors

Abstract Background We investigated plasma YKL-40 levels and chitotriosidase (CHIT1) activity in patients with cystic fibrosis (CF) lung disease and evaluated clinically relevant factors that may affect their levels. Methods Plasma samples were obtained from pediatric (n = 19) and adult patients (n = 15) during exacerbation, discharge and stable period of the disease. YKL-40 levels and chitotriosidase activity were measured by enzyme-linked immunosorbent assay and fluorometric assay, respectively. Data were compared with healthy children and adults of similar age. Results YKL-40 levels of pediatric and adult CF patients at all periods were significantly higher than controls (p < 0.001 and p < 0.05). CHIT1 activities of adult patients at all periods were significantly higher compared to controls (p < 0.05). On the other hand, CHIT1 activities of pediatric CF patients were similar with controls. YKL-40 levels of exacerbation period of adult CF patients were negatively correlated with % FVC (r= -0.800, p = 0.014) and % FEV1 (r= -0.735, p = 0.008). YKL-40 levels in the exacerbation period of pediatric CF patients were negatively correlated with % FVC (r= -0.697, p = 0.0082) and % FEV1 (r= -0.720, p = 0.006). Conclusions CHIT1 activity may be a valuable marker of chronic inflammation in adult CF patients who suffer from CF for a longer period of time compared to pediatric patients. Increased YKL-40 levels in both pediatric and adult patients compared to controls may point to a role in between CF pathology. Furthermore, as YKL-40 levels are correlated with FEV1 and FVC in patients, it may be useful for the monitoring of pulmonary function in CF patient.

In vitro Measurement and In vivo Prediction of Time-Dependent Inhibitory Effects of Three Tyrosine Kinase Inhibitors on CYP3A Activity

2021 ◽  
Vol 22 ◽  
Author(s):  
Liyan Wang ◽  
Tingting Zhao ◽  
Yunxiang Wang ◽  
Banglian Hu ◽  
Jianfei Tao ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Cyp3a Activity ◽  
Drug Drug Interaction ◽  
Inhibitory Potential

Background: Imatinib, sunitinib, and gefitinib are the three most common tyrosine kinase inhibitors (TKIs). However, their quantitative drug-drug interaction potentials In vivo and the relationship between their structure and inhibitory activity remain unknown. Objective: This study aimed to investigate the potential drug-drug interaction risk of three TKIs based on CYP3A. Methods: 6β-Hydroxylated testosterone formation was selected to probe the CYP3A activity in human liver microsomes. Molecular docking simulation was performed to explore the potential structural alerts. Results: Imatinib exhibited the strongest inhibitory effect towards CYP3A, while the inhibitory potential of gefitinib and sunitinib were comparable to each other but weaker than imatinib. IC50 shift assays demonstrated that the inhibitory potential of all three TKIs was significantly increased after a 30-min preincubation with NADPH. The KI and Kinact values of imatinib, sunitinib, and gefitinib were 3.75 μM and 0.055 min–1, 1.96 μM and 0.037 min–1, and 9.94 μM and 0.031 min–1, respectively. IVIVE results showed that there was a 1.3- to 43.1-fold increase in the AUC of CYP3A-metabolizing drugs in the presence of the TKIs. Conclusion: All three TKIs exhibited a typical irreversible inhibitory effect towards CYP3A. The presence of more N-heterocycles and the resulting better binding confirmation of imatinib may have been responsible for its stronger inhibitory effect than sunitinib and gefitinib. Therefore, caution should be taken when CYP3A-metabolizing drugs are co-administrated with imatinib, sunitinib, or gefitinib.

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