| Improvement of renal function with a selective thromboxane A2 synthetase inhibitor, DP-1904, in lupus nephritis. | |
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MedLine Citation:
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PMID: 8895147 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To examine abnormalities of prostanoid metabolism in lupus nephritis, which may affect renal function, and the effects of 4 day dosing of a selective thromboxane A2 (TXA2) synthetase inhibitor, DP-1904, on prostanoid metabolism. METHODS: Urinary levels of various prostanoids, thromboxane B2(TXB2), 11-dehydro-TXB2, 6-keto-prostaglandin F1 alpha, 2,3-dinor-6-keto-PGF1 alpha, and prostaglandin E2 were determined. In a randomized crossover study, 8 patients with biopsy proven lupus nephritis were given 4 days' oral administration of DP-1904 (400 mg/day bid) or indomethacin (50 mg/day bid). The effects of DP-1904 on prostanoid metabolism were studied. RESULTS: Urinary excretion of TXB2, which reflects the renal production of TXA2, was significantly increased in patients with lupus nephritis compared with non-renal systemic lupus erythematosus (SLE)(p < 0.05); enhanced production of TXA2 was also estimated in patients with lupus nephritis. The urinary TXB2/6-keto-PGF1 alpha ratio was also increased in lupus nephritis compared with non-renal SLE (p < 0.01), indicating a prostanoid imbalance that may lead to impaired renal function and subsequent pathology. During administration of DP-1904, the urinary excretion of TXB2 was significantly decreased after 1 to 2 days. An increase in creatinine clearance as a measure of renal function was observed. In contrast, during the administration of indomethacin, urinary excretion of both TXB2 and 6-keto-PGF1 alpha decreased and there were no significant changes in the urinary TXB2/6-keto-PGF1 alpha ratio or creatinine clearance. Hemodynamic changes were associated with a slight increase in sodium excretion, but with no change in arterial blood pressure. No side effects were elicited during the 4 days of treatments. CONCLUSION: The abnormal prostanoid metabolism observed in lupus nephritis could aggravate renal function, which was mediated hemodynamically, and the altered metabolism was reversible and at least partially corrected by a TXA2 synthetase inhibitor, DP-1904. |
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Authors:
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T Yoshida; H Kameda; Y Ichikawa; T Tojo; M Homma |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of rheumatology Volume: 23 ISSN: 0315-162X ISO Abbreviation: J. Rheumatol. Publication Date: 1996 Oct |
Date Detail:
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Created Date: 1997-06-03 Completed Date: 1997-06-03 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 7501984 Medline TA: J Rheumatol Country: CANADA |
Other Details:
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Languages: eng Pagination: 1719-24 Citation Subset: IM |
Affiliation:
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Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Enzyme Inhibitors / therapeutic use* Female Humans Imidazoles / therapeutic use* Indomethacin / therapeutic use Kidney / metabolism* Lupus Nephritis / drug therapy*, metabolism* Middle Aged Prostaglandins / metabolism*, urine Tetrahydronaphthalenes / therapeutic use* Thromboxane A2 / antagonists & inhibitors, therapeutic use Thromboxane-A Synthase / antagonists & inhibitors*, therapeutic use |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Imidazoles; 0/Prostaglandins; 0/Tetrahydronaphthalenes; 53-86-1/Indomethacin; 57576-52-0/Thromboxane A2; 97901-21-8/nafagrel; EC 5.3.99.5/Thromboxane-A Synthase |
| Comments/Corrections | |
Comment In:
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J Rheumatol. 1996 Oct;23(10):1686-8
[PMID:
8895140
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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