Prostaglandin E1 is more effective, when incorporated in lipid microspheres, for treatment of peripheral vascular diseases in man

Mizushima, Yutaka; Yanagawa, Akira; Hoshi, Keiko

doi:10.1111/j.2042-7158.1983.tb02862.x

Cited by 108 publications

(42 citation statements)

References 4 publications

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“…Lipo-PGE 1 , in which PGE 1 was dissolved in lipid microspheres, has succeeded in increasing the clinical efficiency of PGE 1 . [17][18][19] Approximately 90% of PGE 1 exists in the lipid phase in lipo-PGE 1 .…”

Section: Discussionmentioning

confidence: 99%

An Approach to Predict the Ductus-Arteriosus Dilating Effect Induced by Lipo-Prostaglandin E1 in Newborn Rats Lacking Plasma Concentration-Time Data by the Pharmacological Response Kinetic Model.

Yamauchi

Yasunaga

Kawasaki

et al. 2003

Biological & Pharmaceutical Bulletin

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selectively dilate ductus arteriosus in many mammal neonates.1) A cyclodextrin preparation of PGE 1 (PGE 1 -CD)2) and a lipid microsphere preparation of PGE 1 (lipo-PGE 1 ) 3,4) have both been widely used in emergency treatment in neonatal patients with ductus dependent congenital heart diseases (D-CHDs). However, a fatal adverse drug reaction, apnea, may occur when PGE 1 is overdosed.5) Lipo-PGE 1 is a passive targeting-type drug delivery system (DDS) of PGE 1 , in which PGE 1 is dissolved in the lipid emulsion of soybean oil. 6) Momma retorted that the ductus-dilating intensity of lipo-PGE 1 was approximately ten times higher than that of PGE 1 -CD by the clinical monitoring of arterial blood pO 2 in D-CHD patients.3) Thus, lipo-PGE 1 therapy allows for a reduction of the total dose of PGE 1 . Further, the ductus-dilating effect after the discontinuation of lipo-PGE 1 administration lasts much longer than that of PGE 1 -CD. 4,7,8) However, its kinetics have not been clarified from the biopharmaceutical viewpoint. This makes it difficult to present evidence-based precise lipo-PGE 1 therapy in D-CHD patients.Pharmacokinetic analysis based on blood or plasma concentration profiles of drugs has been utilized for optimization of the dosage regimen. Pharmacokinetic/pharmacodynamic (PK/PD) modeling, which is an integrated mathematics model of a pharmacokinetic (concentration-time) and a pharmacodynamic (effect-concentration) event, is a useful tool for predicting the time course of pharmacological response. 9)Ordinary PK/PD modeling studies require validation of both the pharmacokinetic and pharmacodynamic aspects.10) However, it is difficult to obtain both the pharmacokinetic and pharmacodynamic data in, for example, the following cases: as a highly potent drug is administered in quite a low dose, it is difficult to determine plasma concentration of the drug; blood or plasma concentration has no mean in the targetingtype DDS drugs because systemic drug level does not reflect its local pharmacological response. The ductus-dilating effect of PGE 1 has been reported to be extremely potent.1) The clinical dose of lipo-PGE 1 (5 ng/kg/min), a targeting-type DDS, is too low to determine the plasma concentration profiles during the treatment. Thus, in the case of lipo-PGE 1 therapy in D-CHD patients, the acquisition of systemic pharmacokinetic data is technically impossible, and the pharmacokinetic analysis itself is meaningless. In such a case, validation of the model by systemic pharmacokinetic data is impossible, and the only way we can validate the model will be validation by the pharmacological response-time data.In this study, we have assessed changes in the diameter of ductus arteriosus after the bolus i.v. administration of lipo-PGE 1 in a multi-dose study to define a suitable pharmacological response kinetic model (PRK model) and related kinetic parameters. Also, we have investigated whether the model could predict the time course of the ductus-dilating effect under the constant infusion of lipo-PGE 1 . The utility...

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Section: Discussionmentioning

confidence: 99%

An Approach to Predict the Ductus-Arteriosus Dilating Effect Induced by Lipo-Prostaglandin E1 in Newborn Rats Lacking Plasma Concentration-Time Data by the Pharmacological Response Kinetic Model.

Yamauchi

Yasunaga

Kawasaki

et al. 2003

Biological & Pharmaceutical Bulletin

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“…In addition, fever, diarrhea, and hepatic dysfunction have been reported as systemic complications. 14 In order to avoid these problems, PGE1 was mixed with microparticles 0.2 mm in diameter made of soybean oil. Because PGE1 is incorporated into the lipid particles in this preparation, it is less susceptible to inactivation in the lung.…”

Section: Discussionmentioning

confidence: 99%

“…This preparation is not instantaneously inactivated in the body, but it e ciently accumulates in lesions after intravenous injection and releases prostaglandin. 14 Myeloscopic observation was performed from 5 min before administration of PGE1 until 20 min after administration. Morphological changes in the vessels running along the cauda equina and adhesive changes in the cauda equina were observed and were recorded on videotape.…”

Section: Methodsmentioning

confidence: 99%

The effect of Lipo prostaglandin E1 on cauda equina blood flow in patients with lumbar spinal canal stenosis: myeloscopic observation

1999

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Study Design: Myeloscopic examination was performed to observe the cauda equina in patients with lumbar spinal canal stenosis before and after treatment with Lipo prostaglandin E1, a strong peripheral vasodilator. Objectives: The purpose of this study was to clarify the e ects of Lipo prostaglandin E1 on blood¯ow in the cauda equina in patients with lumbar spinal canal stenosis. Setting: Japan, Kagoshima Methods: We performed myeloscopic observations of morphological changes in blood vessels running along the cauda equina in 11 patients with lumbar spinal canal stenosis before and after treatment with Lipo prostaglandin E1. Results: In six of these patients, dilation of the running blood vessels was observed immediately after administration. In all of the patients who exhibited a dilation of vessels on the surface of the cauda equina, intermittent claudication and lower extremity pain and/or numbness lessened immediately after examination. However, none of the patients who exhibited no morphological changes in the vessels along the cauda equina after administration of Lipo prostaglandin E1 experienced any improvement of symptoms at the time of examination. Conclusion: Results of this study suggest that Lipo prostaglandin E1 may enhance blood ow in the cauda equina and improve clinical symptoms in some patients with lumbar spinal stenosis. Sponsorship: None

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“…Therefore there is no worldwide class 1 consensus on PGE1 therapy for ASO patients. Lipo PGE1 (incorporation of PGE1 into soybean oil microspheres with a diameter of 0.2 mm) has been developed to overcome the side-effects of PGE1, 29 but has not been tested in a clinical mega-trial for ASO patients.…”

Section: Discussionmentioning

confidence: 99%

Exercise After Heparin Administration

Maejima

Yasu

Ueba

et al. 2005

Circ J

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he number of patients with arteriosclerosis obliterans (ASO), an atherosclerotic peripheral arterial occlusive disease, is estimated at 500-1,000 individuals per million per year, 1 and the prevalence of intermittent claudication was higher than 1% in a free-living, elderly, North American population. 2 Although bypass operation, stenting and atherectomy are effective therapies for patients with stenosis in the proximal large arteries such as the iliac arteries or femoral arteries, their effects are limited in ASO patients in whom stenotic lesions extend to peripheral small arteries (poor run-off). Enhancement of collateral vessel formation and angiogenesis is a promising therapeutic modality for such non-option ASO patients. Heparin administration reportedly improves the symptoms of ASO Circulation Journal Vol.69, September 2005 patients 9 months after the treatment, 3 and increases the exercise capacity of severe coronary heart disease (CHD) patients by enhancing collateral vessel growth. 4 Recently, investigators have shown that systemic administration of heparin increases the concentration of plasma hepatocyte growth factor (HGF), which promotes neovascularization, [5][6][7] and other studies have shown the effectiveness in ASO and CHD patients of therapeutic angiogenesis using certain growth factors. 8,9 The mechanism of the therapeutic effect of heparin in ASO patients may be strongly related to HGF. There have been no previous studies of whether the combination of an exercise program and heparin administration additionally improves the symptoms of ASO.The aim of the present study was to determine whether a program combining heparin administration with exercise is a useful therapeutic strategy for stimulation of development of collateral circulation in the ischemic legs of patients with non-option ASO. Methods Study PatientsAll subjects had severe chronic limb ischemia that lead to claudication within 400 m of walking. None of the subjects was a candidate for non-surgical or surgical revascularization because of the lack of distal target vessels or for other reasons, such as comorbidities that would increase Background A prospective study examined whether a combination of an exercise program and heparin administration improves the clinical symptoms of patients with arteriosclerosis obliterans (ASO) without an indication for surgical revascularization because of the lack of distal target vessels or other reasons such as high surgical risk or lack of a vein conduit from previous coronary artery bypass surgery. Methods and Results A total of 19 consecutive patients with symptomatic non-option ASO diagnosed by angiography were randomly assigned to 3 groups: heparin + exercise (walking for 60 min after heparin injection [3,000 units/day IV for 14 days], n=6), heparin administration only (n=6), and exercise only (n=7). Plasma levels of hepatocyte growth factor (HGF) were serially measured before and after intravenous administration of heparin. Ankle brachial pressure index was measured and treadmill exercise ...

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Prostaglandin E1 is more effective, when incorporated in lipid microspheres, for treatment of peripheral vascular diseases in man

Abstract: COMMUNICATIONS 0 1983 J. Pharm. Pharmacoi.

Cited by 108 publications

References 4 publications

An Approach to Predict the Ductus-Arteriosus Dilating Effect Induced by Lipo-Prostaglandin E1 in Newborn Rats Lacking Plasma Concentration-Time Data by the Pharmacological Response Kinetic Model.

An Approach to Predict the Ductus-Arteriosus Dilating Effect Induced by Lipo-Prostaglandin E1 in Newborn Rats Lacking Plasma Concentration-Time Data by the Pharmacological Response Kinetic Model.

The effect of Lipo prostaglandin E1 on cauda equina blood flow in patients with lumbar spinal canal stenosis: myeloscopic observation

Exercise After Heparin Administration

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