Formation of 13,14-dihydro-prostaglandin E1 during intravenous infusions of prostaglandin E1 in patients with peripheral arterial occulsive disease

Peskar, Bernhard A.; Hesse, W. H.; Rogatti, W.; Diehm, Curt; Rudofsky, Gottfried; Schweer, Horst; Seyberth, H. W.

doi:10.1016/0090-6980(91)90042-e

Cited by 34 publications

(10 citation statements)

References 9 publications

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“…Endogenous plasma concentrations of PGE1 and its metabolites PGE0 and 15-keto-PGE0 are very low [9][10][11][12]. Therefore analytical methods with high sensitivity and specifity have to be used to describe the pharmacokinetics of PGEa and its metabolites during and after intravenous infusion of PGE> Peskar et al [13] assayed radioimmunologically 15-keto-PGE0 plasma concentrations before, during and after infusion of20, 40 and80 ggPGElwithinl h. Theyfound15-keto-PGE0 plasma concentrations of about 160, 240 and 600 pg.…”

Section: Discussionmentioning

confidence: 99%

“…Recently plasma concentrations of PGE0 in man were reported for the first time [9,10]. For example, Peskar et al, [10] found endogenous PGE0 plasma concentrations of 5 (2) pg-m1-1 and an increase in PGE0 plasma concentrations to 22 (5) pg.…”

Section: Discussionmentioning

confidence: 99%

“…For example, Peskar et al, [10] found endogenous PGE0 plasma concentrations of 5 (2) pg-m1-1 and an increase in PGE0 plasma concentrations to 22 (5) pg. ml-~ during intravenous infusion of 80 .gg PGE: during 1 h. The present data confirm these results and, for the first time, model-dependent parameters of pharmacokinetics are provided.…”

Section: Discussionmentioning

confidence: 99%

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Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects

Cawello

Schweer

Müller

et al. 1994

Eur J Clin Pharmacol

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In a single-blind, randomized, two-way cross-over study with 12 healthy male volunteers, 60 micrograms of prostaglandin E1 (PGE1) or placebo was administered by intravenous infusion during a 120-min period. PGE1, 13,14-dihydro-PGE1 (PGE0) and 15-keto-PGE0 plasma concentrations were measured by a highly specific and sensitive GC-MS/MS method. Endogenous PGE1 plasma concentrations ranged between 1.2 and 1.8 pg.ml-1. Endogenous PGE0 and 15-keto-PGE0 plasma concentrations varied from 0.8 to 1.3 pg.ml-1 and from 4.2 to 6.0 pg/ml respectively. During intravenous infusion of PGE1, plasma PGE1 concentrations rose to a level twice as high as during the placebo infusion. In contrast, PGE0 plasma concentrations were 8 times higher during PGE1 infusion than during placebo infusion, and 15-keto-PGE0 plasma concentrations were 20 times higher. The new analytical method has thus been useful to describe the pharmacokinetics of PGE1 and its metabolites PGE0 and 15-keto-PGE0, during and after intravenous infusion of PGE1.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects

Cawello

Schweer

Müller

et al. 1994

Eur J Clin Pharmacol

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“…At physiological pH, PGI 2 possesses a half-life of approximately 2-3 min [37], which may be sufficiently short to establish an effective gradient of active agent between well-ventilated and nonventilated regions. PGE 1 is a stable compound at neutral pH, is rapidly metabolized to the inactive 13,14-dihydro-15-keto-PGE 1 upon contact with the pulmonary endothelium [38], but may then be reduced back to the 13, 14-dihydro-PGE 1 (PGE 0 ), which again possesses full vasodilatory potency [39,40]. Differences in the conversion from the active agent to inactive metabolites, and possibly also differences in the diffusion characteristics, may thus underlie the superiority of PGI 2 over PGE 1 in optimizing V'/Q' matching.…”

Section: Discussionmentioning

confidence: 99%

Effects of inhaled versus intravenous vasodilators in experimental pulmonary hypertension

Walmrath

Schermuly²,

Pilch³

et al. 1997

Eur Respir J

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Inhaled nitric oxide (NO) causes selective pulmonary vasodilation and improves gas exchange in acute lung failure. In experimental pulmonary hypertension, we compared the influence of the aerosolized vasodilatory prostaglandins (PG) PGI 2 and PGE 1 on vascular tone and gas exchange to that of infused prostanoids (PGI 2 , PGE 1 ) and inhaled NO.An increase of pulmonary artery pressure (Ppa) from 8 to ~34 mmHg was provoked by continuous infusion of U-46619 (thromboxane A 2 (TxA 2 ) analogue) in blood-free perfused rabbit lungs. This was accompanied by formation of moderate lung oedema and severe ventilation-perfusion (V'/Q') mismatch, with predominance of shunt flow (>50%, assessed by the multiple inert gas elimination technique).When standardized to reduce the Ppa by ~10 mmHg, inhaled NO (200 ppm), aerosolized PGI 2 (4 ng·kg -1 ·min -1 ) and nebulized PGE 1 (8 ng·kg -1 ·min -1 ) all reduced both pre-and postcapillary vascular resistance, but did not affect formation of lung oedema. All inhalative agents improved the V '/Q ' mismatch and reduced shunt flow, the rank order of this capacity being NO > PGI 2 > PGE 1 . In contrast, lowering of Ppa by intravascular administration of PGI 2 and PGE 1 did not improve gas exchange. "Supratherapeutic" doses of inhaled vasodilators in control lungs (400 ppm NO, 30 ng·kg -1 ·min -1 of PGI 2 or PGE 1 ) did not provoke vascular leakage or affect the physiological V'/Q' matching.We conclude that aerosolization of prostaglandins I 2 and E 1 is as effective as inhalation of nitric oxide in relieving pulmonary hypertension. When administered via this route instead of being infused intravascularly, the prostanoids are capable of improving ventilation-perfusion matching, suggesting selective vasodilation in well-ventilated lung areas. Eur Respir J 1997; 10: 1084- Inhalation of nitric oxide (NO) has been shown to cause "selective" pulmonary vasodilation, in the absence of vasodilatory effects in the systemic circulation [1][2][3][4]. The different response of gas exchange to NO might be related to the underlying mechanism of ventilation perfusion (V '/Q ') imbalance. In patients with chronic obstructive pulmonary disease (COPD) with broad V '/Q ' heterogeneity, caused by low V '/Q ' ratios but negligible intrapulmonary shunt, NO may worsen gas exchange because of increased perfusion of poorly-ventilated areas [5]. By contrast, in patients with severe adult respiratory distress syndrome (ARDS), in whom shunt flow predominates, the pulmonary vasodilatory effect of inhaled NO was accompanied by an acute improvement of gas exchange [6][7][8]. Due to the transbronchial route, the vasodilatory property of this agent is apparently restricted to well-ventilated lung areas, effecting a redistribution of blood flow from nonventilated regions to these areas. This is considered a substantial progress compared to the intravenous use of vasodilators, such as prostaglandin (PG) I 2 and PGE 1 . These prostanoids provoke nonselective vasodilation both in pulmonary and systemic vessels, and w...

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“…Since an upregulating effect of 13,14-dihydro-PGEl, the biologically active metabolite of PGE1 [23], on LDL receptors has also been found in vitro, these data do not enable conclusions to be drawn as to what extent either the parent compound or its metabolite may have contributed to the beneficial effect seen. The effective dose of PGE1 causing half-maximal alteration in binding as derived from the in vitro results amounts to approximately 50 nmol-1-1.…”

Section: Discussionmentioning

confidence: 67%

Prostaglandin E1 increases binding of 123I-low-density lipoprotein to the human liver in vivo

Sinzinger

Virgolini

Kritz³

et al. 1996

Eur J Clin Pharmacol

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Previous in vitro radioligand binding data have shown that prostaglandin E1 (PGE1) increases the number and the binding affinity of low-density lipoprotein (LDL) receptors of the human liver. Experimental data in normo- and hypercholesterolaemic rabbits have confirmed these findings, showing a significant increase in LDL-binding to the liver in vivo after prolonged PGE1 therapy. METHODS. This study aimed to confirm the experimental and animal data in human in vivo. 123I-LDL binding to the liver was quantified in vivo in patients suffering from peripheral vascular disease, seven of them with heterozygous familial hypercholesterolaemia (HC) and five with normal total plasma cholesterol, after PGE1 administration (5 ng.kg-1.min-1; 6 h daily for 5 days/week for 5 weeks). LDL uptake by the liver was quantified by single photon emission computer tomography (SPECT). RESULTS. The amount of LDL trapped by the liver in normocholesterolaemics (45.6%) was significantly higher than in hypercholesterolaemics (22.0%). PGE1 induced an increase in liver LDL binding, which was more pronounced in HC (+38.2%) than in normocholesterolaemic patients (+8.11%).

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Formation of 13,14-dihydro-prostaglandin E1 during intravenous infusions of prostaglandin E1 in patients with peripheral arterial occulsive disease

Cited by 34 publications

References 9 publications

Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects

Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects

Effects of inhaled versus intravenous vasodilators in experimental pulmonary hypertension

Prostaglandin E1 increases binding of 123I-low-density lipoprotein to the human liver in vivo

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