Pharmacokinetic and pharmacodynamic study of a phospholipid-based phase separation gel for once a month administration of octreotide

Wang, Mengxin; Shan, Fengying; Zou, Yang; Sun, Xun; Zhang, Zhirong; Fu, Yao; Gong, Tao

doi:10.1016/j.jconrel.2016.03.036

Cited by 27 publications

(10 citation statements)

References 60 publications

(66 reference statements)

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“…11 The pharmacokinetics of octreotide have not been evaluated in horses, but the half-life of octreotide acetate solution was 12.6, 0.567, and 0.66 hour in rats, rabbits, and dogs, respectively, when administered via single subcutaneous injection at dosages of 20, 0.025, and 0.022 mg/kg, respectively. 12 Serum insulin concentrations decreased in response to subcutaneous injection of 50 lg SMS 201-995 (octreotide) in healthy human subjects, with subsequent increase in blood glucose concentrations. 13 Octreotide also lowered plasma glucagon concentrations and blunted the nocturnal rise in thyroid-stimulating hormone concentrations, but did not impact thyroid hormone or cortisol concentrations.…”

mentioning

confidence: 88%

“…The elimination half‐life of octreotide is approximately 1.5 hour after intravenous or subcutaneous administration in humans, and octreotide is 20 times more potent than SST when suppressing growth hormone secretion . The pharmacokinetics of octreotide have not been evaluated in horses, but the half‐life of octreotide acetate solution was 12.6, 0.567, and 0.66 hour in rats, rabbits, and dogs, respectively, when administered via single subcutaneous injection at dosages of 20, 0.025, and 0.022 mg/kg, respectively . Serum insulin concentrations decreased in response to subcutaneous injection of 50 μg SMS 201‐995 (octreotide) in healthy human subjects, with subsequent increase in blood glucose concentrations .…”

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confidence: 99%

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Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation

Frank

Hermida

Sanchez-Londoño

et al. 2017

Veterinary Internal Medicne

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BackgroundOctreotide is a somatostatin analog that suppresses insulin secretion.HypothesisWe hypothesized that octreotide would suppress insulin concentrations in horses and that normal (N) horses and those with insulin dysregulation (ID) would differ significantly in their plasma glucose and insulin responses to administration of octreotide.AnimalsTwelve horses, N = 5, ID = 7.MethodsProspective study. An oral sugar test was performed to assign horses to N and ID groups. Octreotide (1.0 μg/kg IV) was then administered, and blood was collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, 75, and 90 minute, and 2, 3, 4, 6, 8, 12, and 24 hour for measurement of glucose and insulin concentrations. Area under the curve (AUC) values were calculated.ResultsMean AUC values for glucose and insulin did not differ between normal (n = 5) and ID (n = 7) groups after octreotide injection. Significant time (P < .001) effects were detected for glucose and insulin concentrations. A group × time interaction (P = .091) was detected for insulin concentrations after administration of octreotide, but the group (P = .33) effect was not significant.Conclusions and Clinical ImportanceOctreotide suppresses insulin secretion, resulting in hyperglycemia, and then concentrations increase above baseline as glycemic control is restored. Our hypothesis that octreotide causes insulin concentrations to decrease in horses was supported, but differences between N and ID groups did not reach statistical significance when blood glucose and insulin responses were compared. The utility of an octreotide response test remains to be determined.

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confidence: 88%

mentioning

confidence: 99%

Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation

Frank

Hermida

Sanchez-Londoño

et al. 2017

Veterinary Internal Medicne

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“…In a previous study [26], OCT PPSG (C OCT = 5 mg/mL) and blank PPSG showed almost the same viscosity at the same temperature, and OCT PPSG transformed into a gel upon exposure to water. Both OCT (octapeptide, Mw = 1019.24) and TP5 (pentapeptide, Mw = 679.77) are low molecular weight peptides, and the drug concentrations in PPSG were relatively low (5 mg/mL).…”

Section: Resultsmentioning

confidence: 74%

“…In vitro release study An in vitro release study was conducted by dynamic dialysis in phosphate-buffered saline containing different concentrations of ethanol (0, 10, and 20%) [25,26]. Aliquots of 0.2 g of TP5-PPSG (TP5 concentration = 5.0 mg/mL) or 1.0 mL of TP5 (TP5 concentration = 1.0 mg/mL) solution were added to the dialysis bags (molecular weight cut-off = 8-14 kDa).…”

Section: Cells and Animalsmentioning

confidence: 99%

Thymopentin-loaded phospholipid-based phase separation gel with long-lasting immunomodulatory effects: in vitro and in vivo studies

et al. 2018

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Thymopentin (TP5) is an effective immunomodulatory agent for autoimmune disease that has been used clinically for decades. However, its application is greatly limited by its extremely short half-life in vivo, poor membrane permeability and extensive metabolism in gastrointestinal tract, resulting in repeated injection and poor patient compliance. In the present study, we developed a TP5-loaded, phospholipid-based phase separation gel (PPSG) to achieve sustained drug release profile and long-lasting therapeutic effects. We firstly demonstrated the physiochemical characteristics of PPSG before and after phase transition by examining the viscosity and morphology change caused by the phase transition. Moreover, the PPSG exerted a low cytotoxicity in L929 cells and HUVECs, suggesting the biocompatibility of PPSG. A month-long drug release profile of TP5 PPSG was observed both in vitro and in vivo, revealing its sustained and controlled drug release property. Most importantly, in cyclophosphamide-induced immunosuppressive rats, a single dose of TP5 PPSG (15 mg/kg, sc) injected could normalize their T-SOD levels and CD4+/CD8+ ratio; such an immunoregulatory effect was comparable to that produced by repeated injection of TP5 solution (0.6 mg/kg per day, sc) for 14 consecutive days. Thus, TP5 PPSG has a great potential for sustained delivery of TP5 in clinical use because of its simple manufacture process, good biocompatibility and long-lasting immunomodulatory efficacy, which could greatly improve patient compliance.

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“…22 Compared with natural somatostatin, OCT shows more advantages, including longer half-life, more metabolic stability, and specificity. 23,24 Honokiol is an active compound isolated from traditional Chinese herb Magnolia officinalis. 25 It exhibits a variety of strong antitumor activities, including pro-apoptotic activity, anti-angiogenesis, anti-metastasis, and anti-proliferation in several types of tumors.…”

Section: Introductionmentioning

confidence: 99%

Application of multifunctional targeting epirubicin liposomes in the treatment of non-small-cell lung cancer

Song

Xiao

et al. 2017

IJN

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Chemotherapy for aggressive non-small-cell lung cancer (NSCLC) usually results in a poor prognosis due to tumor metastasis, vasculogenic mimicry (VM) channels, limited killing of tumor cells, and severe systemic toxicity. Herein, we developed a kind of multifunctional targeting epirubicin liposomes to enhance antitumor efficacy for NSCLC. In the liposomes, octreotide was modified on liposomal surface for obtaining a receptor-mediated targeting effect, and honokiol was incorporated into the lipid bilayer for inhibiting tumor metastasis and eliminating VM channels. In vitro cellular assays showed that multifunctional targeting epirubicin liposomes not only exhibited the strongest cytotoxic effect on Lewis lung tumor cells but also showed the most efficient inhibition on VM channels. Action mechanism studies showed that multifunctional targeting epirubicin liposomes could downregulate PI3K, MMP-2, MMP-9, VE-Cadherin, and FAK and activate apoptotic enzyme caspase 3. In vivo results exhibited that multifunctional targeting epirubicin liposomes could accumulate selectively in tumor site and display an obvious antitumor efficacy. In addition, no significant toxicity of blood system and major organs was observed at a test dose. Therefore, multifunctional targeting epirubicin liposomes may provide a safe and efficient therapy strategy for NSCLC.

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Pharmacokinetic and pharmacodynamic study of a phospholipid-based phase separation gel for once a month administration of octreotide

Cited by 27 publications

References 60 publications

Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation

Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation

Thymopentin-loaded phospholipid-based phase separation gel with long-lasting immunomodulatory effects: in vitro and in vivo studies

Application of multifunctional targeting epirubicin liposomes in the treatment of non-small-cell lung cancer

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