A thromboxane A2 synthase inhibitor, DP-1904, prevents rat renal injury

Masumura, Hidemi; Kunitada, Satoshi; Irie, Kiyoshi; Ashida, Shinji; Abe, Youichi

doi:10.1016/0014-2999(91)90146-h

Cited by 15 publications

(9 citation statements)

References 21 publications

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“…10 In animal models, platelet activation contributes to ischemic glomerular injury, 11 whereas inhibition reduces injury. 12 Whether abciximab confers a benefit during renal stenting is untested. In addition, the utility of abciximab combined with EPDs remains unclear.…”

Section: Editorial P 2724 Clinical Perspective P 2760mentioning

confidence: 99%

“…Certainly, the renal circulation is sensitive to microvascular events, presumably because of the vascular architecture of the cortical glomeruli and the microvasculature of the peritubular medulla. Now it appears that prior work suggesting a role for platelet activation in ischemia-induced renal dysfunction 11,12 may have relevance to stenting. It also raises concerns that capturing emboli may not be an adequate surrogate for clinical outcome.…”

Section: Interaction Of Angioguard and Abciximabmentioning

confidence: 99%

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Embolic Protection and Platelet Inhibition During Renal Artery Stenting

et al. 2008

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Background-Preservation of renal function is an important objective of renal artery stent procedures. Although atheroembolization can cause renal dysfunction during renal stent procedures, whether adjunctive use of embolic protection devices or glycoprotein IIb/IIIa inhibitors improves renal function is unknown. Methods and Results-One hundred patients undergoing renal artery stenting at 7 centers were randomly assigned to an open-label embolic protection device, Angioguard, or double-blind use of a platelet glycoprotein IIb/IIIa inhibitor, abciximab, in a 2ϫ2 factorial design. The main effects of treatments and their interaction were assessed on percentage change in Modification in Diet in Renal Disease-derived glomerular filtration rate from baseline to 1 month using centrally analyzed creatinine. Filter devices were analyzed for the presence of platelet-rich thrombus. With stenting alone, stenting and embolic protection, and stenting with abciximab alone, glomerular filtration rate declined (PϽ0.05), but with combination therapy, it did not decline and was superior to the other allocations in the 2ϫ2 design (PϽ0.01). The main effects of treatment demonstrated no overall improvement in glomerular filtration rate; although abciximab was superior to placebo (0Ϯ27% versus Ϫ10Ϯ20%; PϽ0.05), embolic protection was not (Ϫ1Ϯ28% versus Ϫ10Ϯ20%; Pϭ0.08). An interaction was observed between abciximab and embolic protection (PϽ0.05), favoring combination treatment. Abciximab reduced the occurrence of platelet-rich emboli in the filters from 42% to 7% (PϽ0.01). Conclusions-Renal artery stenting alone, stenting with embolic protection, and stenting with abciximab were associated with a decline in glomerular filtration rate. An unanticipated interaction between Angioguard and abciximab was seen, with combination therapy better than no treatment or either treatment alone. (Circulation. 2008;117:2752-2760.)

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Section: Editorial P 2724 Clinical Perspective P 2760mentioning

confidence: 99%

Section: Interaction Of Angioguard and Abciximabmentioning

confidence: 99%

Embolic Protection and Platelet Inhibition During Renal Artery Stenting

et al. 2008

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“…These studies showed that TXA, is a potent renal vasoconstrictor and that its production is increased in both hydronephrosis and acute renal failure, resulting in further impairment of renal function. DP-1904 may improve renal function by suppressing the excessive renal production of TXA,, thereby increasing the 6-keto-PGF,,/TXB2 ratio (23).…”

Section: Effect On Rat Hydronephrosis Model or Rat Ischemic Acute Renmentioning

confidence: 99%

“…The effects of DP-1904 on renal function were investigated by analysis of prostanoid metabolism in hydronephrotic rat kidney models (23). Male Sprague-Dawley rats were used to prepare the hydronephrosis model according to the method of Whinnery et a1 (43).…”

Section: Effect On Rat Hydronephrosis Model or Rat Ischemic Acute Renmentioning

confidence: 99%

“…Selective inhibition of thromboxane synthesis offers a possible new therapeutic approach to those disease states in which increased thromboxane formation is critically involved. DP-1904 is a novel imidazole-type TXA, synthetase inhibitor; it produces a selective, potent and long-acting inhibition of TXA, synthesis (12,17,40), and it has a protective effect against experimental myocardial ischemia, asthma, and hydronephrosis (23,38,41). In this review, we will discuss the in vitro and in vivo pharmacology of DP-1904, studies in animal models, and data from clinical studies.…”

Section: Introductionmentioning

confidence: 99%

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DP‐1904: A Novel Specific TXA₂ Synthetase Inhibitor

Ishizuka

1997

Cardiovascular Drug Reviews

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Pharmacokinetic-pharmacodynamic modelling of DP-1904, a novel thromboxane synthetase inhibitor in rabbits, based on an indirect response model

Zheng

Sato

Adachi

et al. 1996

European Journal of Drug Metabolism and Pharmacokinetics

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A new imidazole derivative, DP-1904, produces a selective, potent and long-acting inhibition of thromboxane A2 (TXA2) syntheses and platelet aggregation. This study was designed to investigate the pharmacokinetics and pharmacodynamics (PK/PD) of DP-1904. DP-1904 disappeared from plasma with a half-life of 20 min after i.v. dosing, and the bioavailability after oral dosing was approximately 70%. The level of serum TXB2, which is a pharmacological marker for thromboxane synthetase inhibition, was measured to characterize the pharmacodynamics of DP-1904. A marked reduction of serum TXB2 was exhibited within 1 h after both i.v. and oral doses, reflecting the rapid onset of action of DP-1904. Serum TXB2 returned to the basal level much more slowly after oral dosing than after i.v. dosing, due to the longer half-life after oral dosing. An Emax model was employed to fit the pharmacological data after oral dosing, and IC50 and Emax values were estimated to be 5.0 ng/ml and 81%, respectively. In order to test its predictability, the PK/PD model was then used to predict a pharmacological profile after i.v. dosing; good agreement between the observed and predicted values was achieved. Thus, the present modelling procedure may be useful for optimizing the therapeutic regimens of DP-1904.

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A thromboxane A2 synthase inhibitor, DP-1904, prevents rat renal injury

Cited by 15 publications

References 21 publications

Embolic Protection and Platelet Inhibition During Renal Artery Stenting

Embolic Protection and Platelet Inhibition During Renal Artery Stenting

DP‐1904: A Novel Specific TXA₂ Synthetase Inhibitor

Pharmacokinetic-pharmacodynamic modelling of DP-1904, a novel thromboxane synthetase inhibitor in rabbits, based on an indirect response model

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A thromboxane A2 synthase inhibitor, DP-1904, prevents rat renal injury

Cited by 15 publications

References 21 publications

Embolic Protection and Platelet Inhibition During Renal Artery Stenting

Embolic Protection and Platelet Inhibition During Renal Artery Stenting

DP‐1904: A Novel Specific TXA2 Synthetase Inhibitor

Pharmacokinetic-pharmacodynamic modelling of DP-1904, a novel thromboxane synthetase inhibitor in rabbits, based on an indirect response model

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DP‐1904: A Novel Specific TXA₂ Synthetase Inhibitor