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  1. Patel RP, Jacob J, Sedeeq M, Ming LC, Wanandy T, Zaidi STR, et al.
    Clin Ther, 2018 04;40(4):664-667.
    PMID: 29496321 DOI: 10.1016/j.clinthera.2018.02.009
    PURPOSE: The aim was to investigate the stability of cefazolin in elastomeric infusion devices.

    METHODS: Elastomeric devices (Infusor LV) that contain cefazolin (3 g/240 mL and 6 g/240 mL) were prepared and stored at 4°C for 72 hours and then at 35°C for 12 hours, followed by 25°C for 12 hours. An aliquot was withdrawn at predefined time points and analyzed for the concentration of cefazolin. Samples were also assessed for changes in pH, solution color, and particle content.

    FINDINGS: Cefazolin retained acceptable chemical and physical stability over the studied storage period and conditions.

    IMPLICATIONS: These findings will allow the administration of cefazolin by the Infusor LV elastomeric device in the outpatient and remote settings.

  2. Al Madfai F, Valah B, Zaidi STR, Wanandy T, Ming LC, Peterson GM, et al.
    J Clin Pharm Ther, 2018 Aug;43(4):530-535.
    PMID: 29500838 DOI: 10.1111/jcpt.12674
    WHAT IS KNOWN AND OBJECTIVE: Continuous infusion of dobutamine plays an important role in the management of patients with end-stage heart failure. Home infusion of dobutamine using a continuous ambulatory delivery device (CADD) facilitates the management of patients in their home, avoiding complications associated with long-term hospitalization. However, the stability of dobutamine in CADD is currently unknown. Therefore, this study investigated the physicochemical stability of dobutamine in CADDs at three different temperatures over various time points.

    METHODS: Six CADDs (three containing dobutamine 10 mg/mL in 0.9% sodium chloride and three containing dobutamine 10 mg/mL in 5% glucose) were prepared and stored at 4°C for 7 days, followed by 12 hours at 35°C and then for another 12 hours at 25°C. An aliquot (n = 3) was withdrawn aseptically at 0, 24, 48, 72, 96, 120, 144 and 168 hours when stored at 4°C, and at 0, 6 and 12 hours when stored at the other two temperatures. Each sample was analysed for dobutamine concentration using a stability-indicating high-performance liquid chromatography. All the samples were also evaluated for change in pH, colour and for particle content.

    RESULTS AND DISCUSSION: No evidence of particle formation, colour or pH change was observed throughout the study period. Dobutamine, when admixed with 0.9% sodium chloride or 5% glucose, was found to be chemically stable for at least 168 hours at 4°C and for another 12 hours at 35°C and for another 12 hours at 25°C.

    WHAT IS NEW AND CONCLUSIONS: Our findings will allow health professionals to provide a weekly supply of dobutamine-containing CADDs to patients for home infusions. Continuous infusion over a 24-hour period using one CADD per day will also decrease the number of exchanges required and thus reduce the risk of catheter-related bloodstream infections.

  3. Patel RP, Shastri MD, Ming LC, Zaidi STR, Peterson GM
    Front Pharmacol, 2018;9:586.
    PMID: 29922163 DOI: 10.3389/fphar.2018.00586
    Lichen planus (LP) is an uncommon mucocutaneous inflammatory condition, that is immunologically mediated, typically pruritic and often recurs. The currently advocated therapies are either not highly effective or associated with severe side effects. Enoxaparin, a widely used anticoagulant, is composed of both anticoagulant and non-anticoagulant fragments. Enoxaparin is reported to have anti-inflammatory properties and it was found to be effective in LP. However, the results from clinical studies have varied substantially and, therefore, the clinical role of enoxaparin in LP remains uncertain. This review focuses on potential reasons for the reported inconsistent outcomes, as well as proposing solutions; these include identifying batch-to-batch inconsistency in the composition of enoxaparin. The potential therapeutic value of enoxaparin in LP must be explored using well-designed clinical trials, combined with experimental studies that focus on identifying the anti-inflammatory fragments of enoxaparin and elucidating the mechanism of action of these non-anticoagulant fragments.
  4. Lean QY, Gueven N, Eri RD, Bhatia R, Sohal SS, Stewart N, et al.
    Expert Rev Clin Pharmacol, 2015;8(6):795-811.
    PMID: 26308504 DOI: 10.1586/17512433.2015.1082425
    Current drug therapies for ulcerative colitis (UC) are not completely effective in managing moderate-to-severe UC and approximately 20% of patients with severe UC require surgical interventions. Heparins, polydisperse mixtures of non-anticoagulant and anticoagulant oligosaccharides, are widely used as anticoagulants. However, heparins are also reported to have anti-inflammatory properties. Unfractionated heparin was initially used in patients with UC for the treatment of rectal microthrombi. Surprisingly, it was found to be effective in reducing UC-associated symptoms. Since then, several pre-clinical and clinical studies have reported promising outcomes of heparins in UC. In contrast, some controlled clinical trials demonstrated no or only limited benefits, thus the potential of heparins for the treatment of UC remains uncertain. This review discusses potential mechanisms of action of heparins, as well as proposed reasons for their contradictory clinical effectiveness in the treatment of UC.
  5. Lean QY, Eri RD, Randall-Demllo S, Sohal SS, Stewart N, Peterson GM, et al.
    PLoS One, 2015;10(7):e0134259.
    PMID: 26218284 DOI: 10.1371/journal.pone.0134259
    Inflammatory bowel diseases, such as ulcerative colitis, cause significant morbidity and decreased quality of life. The currently available treatments are not effective in all patients, can be expensive and have potential to cause severe side effects. This prompts the need for new treatment modalities. Enoxaparin, a widely used antithrombotic agent, is reported to possess anti-inflammatory properties and therefore we evaluated its therapeutic potential in a mouse model of colitis. Acute colitis was induced in male C57BL/6 mice by administration of dextran sulfate sodium (DSS). Mice were treated once daily with enoxaparin via oral or intraperitoneal administration and monitored for colitis activities. On termination (day 8), colons were collected for macroscopic evaluation and cytokine measurement, and processed for histology and immunohistochemistry. Oral but not intraperitoneal administration of enoxaparin significantly ameliorated DSS-induced colitis. Oral enoxaparin-treated mice retained their body weight and displayed less diarrhea and fecal blood loss compared to the untreated colitis group. Colon weight in enoxaparin-treated mice was significantly lower, indicating reduced inflammation and edema. Histological examination of untreated colitis mice showed a massive loss of crypt architecture and goblet cells, infiltration of immune cells and the presence of edema, while all aspects of this pathology were alleviated by oral enoxaparin. Reduced number of macrophages in the colon of oral enoxaparin-treated mice was accompanied by decreased levels of pro-inflammatory cytokines. Oral enoxaparin significantly reduces the inflammatory pathology associated with DSS-induced colitis in mice and could therefore represent a novel therapeutic option for the management of ulcerative colitis.
  6. Shastri MD, Chong WC, Dua K, Peterson GM, Patel RP, Mahmood MQ, et al.
    Inflammopharmacology, 2021 Feb;29(1):15-33.
    PMID: 33152094 DOI: 10.1007/s10787-020-00770-y
    Asthma is a common, heterogeneous and serious disease, its prevalence has steadily risen in most parts of the world, and the condition is often inadequately controlled in many patients. Hence, there is a major need for new therapeutic approaches. Mild-to-moderate asthma is considered a T-helper cell type-2-mediated inflammatory disorder that develops due to abnormal immune responses to otherwise innocuous allergens. Prolonged exposure to allergens and persistent inflammation results in myofibroblast infiltration and airway remodelling with mucus hypersecretion, airway smooth muscle hypertrophy, and excess collagen deposition. The airways become hyper-responsive to provocation resulting in the characteristic wheezing and obstructed airflow experienced by patients. Extensive research has progressed the understanding of the underlying mechanisms and the development of new treatments for the management of asthma. Here, we review the basis of the disease, covering new areas such as the role of vascularisation and microRNAs, as well as associated potential therapeutic interventions utilising reports from animal and human studies. We also cover novel drug delivery strategies that are being developed to enhance therapeutic efficacy and patient compliance. Potential avenues to explore to improve the future of asthma management are highlighted.
  7. Shastri MD, Allam VSRR, Shukla SD, Jha NK, Paudel KR, Peterson GM, et al.
    Life Sci, 2021 Oct 15;283:119871.
    PMID: 34352260 DOI: 10.1016/j.lfs.2021.119871
    Non-communicable, chronic respiratory diseases (CRDs) affect millions of individuals worldwide. The course of these CRDs (asthma, chronic obstructive pulmonary disease, and cystic fibrosis) are often punctuated by microbial infections that may result in hospitalization and are associated with increased risk of morbidity and mortality, as well as reduced quality of life. Interleukin-13 (IL-13) is a key protein that regulates airway inflammation and mucus hypersecretion. There has been much interest in IL-13 from the last two decades. This cytokine is believed to play a decisive role in the exacerbation of inflammation during the course of viral infections, especially, in those with pre-existing CRDs. Here, we discuss the common viral infections in CRDs, as well as the potential role that IL-13 plays in the virus-induced disease pathogenesis of CRDs. We also discuss, in detail, the immune-modulation potential of IL-13 that could be translated to in-depth studies to develop IL-13-based therapeutic entities.
  8. Chong WC, Chellappan DK, Shukla SD, Peterson GM, Patel RP, Jha NK, et al.
    Viruses, 2021 Jul 18;13(7).
    PMID: 34372603 DOI: 10.3390/v13071397
    The recent coronavirus disease 2019 (COVID-19) outbreak has drawn global attention, affecting millions, disrupting economies and healthcare modalities. With its high infection rate, COVID-19 has caused a colossal health crisis worldwide. While information on the comprehensive nature of this infectious agent, SARS-CoV-2, still remains obscure, ongoing genomic studies have been successful in identifying its genomic sequence and the presenting antigen. These may serve as promising, potential therapeutic targets in the effective management of COVID-19. In an attempt to establish herd immunity, massive efforts have been directed and driven toward developing vaccines against the SARS-CoV-2 pathogen. This review, in this direction, is aimed at providing the current scenario and future perspectives in the development of vaccines against SARS-CoV-2.
  9. Mendes K, Harmanjeet H, Sedeeq M, Modi A, Wanandy T, Zaidi STR, et al.
    Perit Dial Int, 2018 07 10;38(6):430-440.
    PMID: 29991562 DOI: 10.3747/pdi.2017.00274
    BACKGROUND: Infections caused by ceftazidime-resistant Pseudomonas and extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacteria are increasing worldwide. Meropenem and piperacillin/tazobactam (PIP/TZB) are recommended for the treatment of peritoneal dialysis-associated peritonitis (PDAP) caused by ceftazidime-resistant Pseudomonas and other resistant gram-negative bacteria. Patients may also receive intraperitoneal heparin to prevent occlusion of their catheters. However, the stability of meropenem or PIP/TZB, in combination with heparin, in different types of peritoneal dialysis (PD) solutions used in clinical practice is currently unknown. Therefore, we investigated the stability of meropenem and PIP/TZB, each in combination with heparin, in different PD solutions.

    METHODS: A total of 15 PD bags (3 bags for each type of PD solution) containing meropenem and heparin and 24 PD bags (3 bags for each type of PD solution) containing PIP/TZB and heparin were prepared and stored at 4°C for 168 hours. The same bags were stored at 25°C for 3 hours followed by 10 hours at 37°C. An aliquot withdrawn before storage and at defined time points was analyzed for the concentration of meropenem, PIP, TZB, and heparin using high-performance liquid chromatography. Samples were also analysed for particle content, pH and color change, and the anticoagulant activity of heparin.

    RESULTS: Meropenem and heparin retained more than 90% of their initial concentration in 4 out of 5 types of PD solutions when stored at 4°C for 168 hours, followed by storage at 25°C for 3 hours and then at 37°C for 10 hours. Piperacillin/tazobactam and heparin were found to be stable in all 8 types of PD solutions when stored under the same conditions. Heparin retained more than 98% of its initial anticoagulant activity throughout the study period. No evidence of particle formation, color change, or pH change was observed at any time under the storage conditions employed in the study.

    CONCLUSIONS: This study provides clinically important information on the stability of meropenem and PIP/TZB, each in combination with heparin, in different PD solutions. The use of meropenem-heparin admixed in pH-neutral PD solutions for the treatment of PDAP should be avoided, given the observed suboptimal stability of meropenem.

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