Role of metformin in various pathologies: state-of-the-art microcapsules for improving its pharmacokinetics

2020 ◽  
Vol 11 (11) ◽  
pp. 733-753
Author(s):  
Ahmed Gedawy ◽  
Hani Al-Salami ◽  
Crispin R Dass
Keyword(s):  
Oral Bioavailability ◽  
Delivery Systems ◽  
First Line ◽  
Flip Flop ◽  
Therapeutic Goals ◽  
First Line Therapy ◽  
Particulate Delivery ◽  
Potential Tool

Metformin was originally derived from a botanical ancestry and became the most prescribed, first-line therapy for Type 2 diabetes in most countries. In the last century, metformin was discovered twice for its antiglycemic properties in addition to its antimalarial and anti-influenza effects. Metformin exhibits flip-flop pharmacokinetics with limited oral bioavailability. This review outlines metformin pharmacokinetics, pharmacodynamics and recent advances in polymeric particulate delivery systems as a potential tool to target metformin delivery to specific tissues/organs. This interesting biguanide is being rediscovered this century for multiple clinical indications as anticancer, anti-aging, anti-inflammatory, anti-Alzheimer’s and much more. Microparticulate delivery systems of metformin may improve its oral bioavailability and optimize the therapeutic goals expected.

Insulin as a First-Line Therapy in Type 2 Diabetes: Should the use of sulfonylureas be halted?

Diabetes Care ◽  
2008 ◽  
Vol 31 (Supplement 2) ◽  
pp. S136-S139 ◽  
Author(s):  
E. Standl ◽  
O. Schnell
Keyword(s):  
Type 2 Diabetes ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

scholarly journals Practical Aspects of Interface Application in CPAP Treatment

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Adel Bachour ◽  
Heidi Avellan-Hietanen ◽  
Tuula Palotie ◽  
Paula Virkkula
Keyword(s):  
Airway Pressure ◽  
Positive Airway Pressure ◽  
Medical Team ◽  
Cpap Therapy ◽  
Air Leak ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Nasal Stuffiness

While continuous positive airway pressure (CPAP) is an effective first-line therapy for sleep apnea, CPAP fails in one third of patients mainly due to poor adherence to the CPAP device and masks. The role of the medical team is to guide the patient in choosing the best mask, thus insuring good CPAP therapy adherence. Once a suitable mask is found, the brand of the mask does not affect patient satisfaction or CPAP adherence. For the majority of patients, nasal masks are by far more suitable than oronasal masks. Orosanal masks are indicated in case of nasal stuffiness or when an air leak manifests through the mouth. Re-evaluation of the efficacy of CPAP therapy is recommended when switching to oronasal masks.

Reversal of Resistance to Doxifluridine and Fluorouracil in Metastatic Colorectal Cancer: The Role of High-Dose Folinic Acid

1992 ◽  
Vol 78 (4) ◽  
pp. 258-261 ◽  
Author(s):  
Marco Colleoni ◽  
Emilio Bajetta ◽  
Filippo de Braud ◽  
Nicoletta Zilembo ◽  
Franco Noiè ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Folinic Acid ◽  
Performance Status ◽  
Objective Response ◽  
High Dose ◽  
Severe Toxicity ◽  
First Line ◽  
First Line Therapy ◽  
Colon And Rectum

The benefits from medical treatment in colorectal cancer are limited. Fluorouracil remains the only recognized drug, and how to treat unresponsive patients is still debated. To evaluate the role of folinic acid (FA) in circumvence resistance in colorectal cancer, 28 patients pretreated with fluoropyrimidine were candidated to receive one of the following schedules: fluorouracil (600 mg/m2) associated with FA (500 mg/m2) weekly for 6 weeks (Regimen A: 21 cases), or fluorouracil (370 mg/m2) plus FA (200 mg/m2) dally for 5 days every 4 weeks (Regimen B: 7 cases). Fourteen patients were pretreated with doxifluridlne, a new fluoropyrimldine derivative with a peculiar mechanism of action, and the remaining 14 patients with fluorouracil. All but 2 patients were unresponsive to first-line treatments. When the treatment began, the median age of the patients was 60 years (range, 30-68). The performance status (ECOG) was 0/1 in 25 of them, and the primary tumor was in the colon and rectum in 19 and 9 patients, respectively. Sites of disease were liver (64 %), lung (35 %), local recurrence (10 %) and peritoneum (10 %). A median of 3 cycles (range, 1-7) was delivered, and no objective response was observed in the group of patients pretreated with doxlfluridine or in the group pretreated with fluorouracil. In 5 cases a significant decrease in baseline CEA values was observed. Therapy was well tolerated, and no grade 4 toxicity was encountered. Severe toxicity was limited and included diarrhea (7 patients), stomatitis (1 patient) and nausea/vomiting (1 patient). High-dose FA has no role in reversing resistance to fluoropyrimidine, and other mechanisms of refractoriness are surely involved. FA should be associated with fluoropyrimidine as first-line therapy together with other biochemical modulators. Further rescue therapies need to be developed.

Rationale and design of a clinical trial to evaluate metformin and colesevelam HCl as first-line therapy in type 2 diabetes and colesevelam HCl in prediabetes

2009 ◽  
Vol 25 (9) ◽  
pp. 2239-2249 ◽  
Author(s):  
Michael R. Jones ◽  
Sunder Mudaliar ◽  
Eric Hernandez-Triana ◽  
Ambika G. Unnikrishnan ◽  
Yu-Ling Lai ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Clinical Trial ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

scholarly journals Endovascular management of spinal vascular malformations: history and literature review

2009 ◽  
Vol 26 (1) ◽  
pp. E7 ◽  
Author(s):  
Ricky Medel ◽  
R. Webster Crowley ◽  
Aaron S. Dumont
Keyword(s):  
Endovascular Therapy ◽  
Surgical Intervention ◽  
Vascular Malformations ◽  
Therapeutic Tool ◽  
First Line ◽  
Spinal Vascular Malformations ◽  
First Line Therapy ◽  
Treatment Paradigm ◽  
The 1960S

Spinal vascular malformations represent a complex group of entities whose treatment paradigm continually evolves. Given the ever-increasing role of endovascular therapy, it is the goal of the authors to review the current literature regarding this therapeutic tool and to provide recommendations guiding management. A thorough literature search was conducted using Medline, with subsequent articles being identified through cross-referencing. The analysis revealed that, since its introduction in the 1960s, endovascular therapy has been used to manage the entire spectrum of spinal vascular malformations, during which period it has undergone considerable technological and technical evolution. As such, embolization has proved of growing therapeutic utility, largely resulting from the mounting evidence supporting its safety and efficacy, in addition to the inherent minimally invasive nature. This alternative to surgical intervention will be increasingly used as first-line therapy in spinal vascular malformations.

KIT and PDGFRAmutation status and their immunohistochemical (IHC) expression profile of gastrointestinal stromal tumor (GIST) patients treated with imatinib (IMT): Seven-year single-center experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10558-10558
Author(s):  
Y. Koh ◽  
H. Kim ◽  
H. Lee ◽  
K. Lee ◽  
D. Oh ◽  
...  
Keyword(s):  
Treatment Outcome ◽  
First Line ◽  
Mutation Status ◽  
Single Center Experience ◽  
First Line Therapy ◽  
Positive Rate ◽  
Exon 11 ◽  
Tumor Dna

10558 Background: Previous studies suggested the role of KIT and PDGFRAmutations on treatment outcome of GIST with IMT, but results are heterogeneous. IHC value of PDGFRA and PDGFRB is not established. Methods: We included patients (pts) treated with IMT as a first line therapy for metastastic or relapsed GIST between 2001 and 2008. Tumor DNA was extracted to investigate the mutation status of KITexon 9, exon 11, PDGFRA exon 12 and 18. IHC stain of c-KIT and PDGFRA/B was performed. We assessed the correlation between the treatment outcome, genetic status and IHC results. Results: A total of 85 pts (M:F=49:36, median age 58.4 years) received IMT 400 mg daily. Location of primary disease included stomach (33), small bowel (34), rectum (10), esophagus (1), and omentum/mesentery (7). Complete and partial responses were achieved in 6% and 62% of pts respectively, while 5% of pts had progressive disease. During median follow up of 28.1 months, estimated median PFS was 39.8 months. KIT exon 11 and 9 mutations were detected in 64% and 5% respectively. Exon 11 mutations included 44 deletions, 2 insertions, 5 substitutions and 3 deletion/insertions. PDGFRA exon 12 and 18 mutations were detected in 2% respectively. Positive rate of c-KIT, PDGFRA and PDGFRB using IHC was 96%, 21%, and 26% respectively. PDGFRA and PDGFRB were co-expressed (p=0.001). PDGFRA mutation did not correlate with PDGFRA/B expression. Clinical response was not different according to the mutation status or IHC expression. PFS of KIT exon 11, KITexon 9, PDGFRA mutants and pts without detectable mutations were not different (p=0.397). Pts with KIT exon 11 balanced mutations (substitution or deletion/insertion) showed longer PFS compared with pts with unbalanced mutations (deletion or insertion) (p=0.014) or pts without exon 11 mutations (p=0.033). Median PFS was shorter in pts lacking c-KIT (p=0.001) expression. PDGFRA/B expression did not influence PFS. Conclusions: Balanced mutation of KIT exon 11 predicted longer PFS, while lack of c-KIT protein expression predicted shorter PFS for GIST pts treated with first line IMT. PDGFRA and B were co-expressed without predictive value. No significant financial relationships to disclose.

Progression-free survival in patients with cholangiocarcinoma with FGFR2 fusions or rearrangements: An exploration of response to systemic therapy.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. 588-588 ◽  
Author(s):  
Kristen Bibeau ◽  
Luis Féliz ◽  
Scott Barrett ◽  
Ling Na ◽  
Christine Francis Lihou ◽  
...  
Keyword(s):  
Systemic Therapy ◽  
Progression Free Survival ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Free Survival ◽  
Prior Therapy ◽  
First Line Therapy ◽  
Line Therapy

588 Background: Most cholangiocarcinoma (CCA) patients (pts) are diagnosed with advanced disease and are ineligible for surgery. FGFR2 fusions or rearrangements are present in 10–16% of pts with intrahepatic CCA (iCCA) and are reported to be oncogenic drivers. However, little data are available on the role of FGFR2 genetic alterations in the response to systemic cancer therapy. FIGHT-202 is a phase 2 study of pemigatinib (a selective, potent, oral FGFR1–3 inhibitor) in pts with previously treated advanced/metastatic CCA (NCT02924376); primary results were reported at ESMO 2019. FIGHT-202 enrolled pts who progressed on ≥1 prior therapy, allowing the examination of the role of FGFR2 alterations on the response to prior therapy. The objective of this post hoc analysis was to evaluate progression free survival (PFS) on standard systemic therapy received prior to study enrollment among pts with CCA harboring FGFR2 fusions or rearrangements ( FGFR2+). Methods: Case report forms were reviewed to determine disease history and exposure to prior lines of systemic cancer therapies (LOSCT) in the advanced setting before receiving pemigatinib. Only pts with sufficient data on prior LOSCT were included in this analysis. Median PFS was calculated using the Kaplan-Meier method. Results: 102 pts were included in this analysis (median age 54.5, 61.8% female). Median PFS on first-line therapy was 5.5 (95% CI: 4.0, 8.0) months. Among the 38 pts (37.3%) with ≥2 prior LOSCT, median PFS on second-line therapy was 4.4 (95% CI: 3.0, 5.3) months. Conclusions: This analysis provides data about PFS on standard systemic therapies for pts with FGFR2+ CCA. Median PFS on first-line therapy was lower than historical published data, and median PFS on second-line therapy was slightly longer than previously reported, in unselected CCA populations. Limitations of this analysis include retrospective examination of investigator reported data, and that clinical trial participants may not truly reflect a general CCA patient population. The short PFS on standard therapies in pts with FGFR2+ CCA highlights the need for development of other options including targeted therapies to improve outcomes.

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