Document Detail


Improvement of renal function with a selective thromboxane A2 synthetase inhibitor, DP-1904, in lupus nephritis.
MedLine Citation:
PMID:  8895147     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
T Yoshida; H Kameda; Y Ichikawa; T Tojo; M Homma
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of rheumatology     Volume:  23     ISSN:  0315-162X     ISO Abbreviation:  J. Rheumatol.     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1997-06-03     Completed Date:  1997-06-03     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7501984     Medline TA:  J Rheumatol     Country:  CANADA    
Other Details:
Languages:  eng     Pagination:  1719-24     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
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:
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:
J Rheumatol. 1996 Oct;23(10):1686-8   [PMID:  8895140 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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