Effects of short-term treatment with diclofenac-colestyramine on renal function and urinary prostanoid excretion in patients with type-2 diabetes.
OBJECTIVE
To determine the effect of short-term administration of diclofenac-colestyramine on glomerular filtration rate (GFR), renal plasma flow (RPF) and urinary excretion of prostanoids in patients with type-2 diabetes without and with impaired renal function.


METHODS
In the randomised, single-blind, placebo-controlled, two-period crossover study, 32 patients with type-2 diabetes (group 1: 16 patients without impaired renal function, creatinine clearance > or =80 ml/min and group 2: 16 patients with impaired renal function, creatinine clearance 30-79 ml/min) received 140 mg diclofenac-colestyramine (corresponding to 75 mg diclofenac sodium) or placebo twice a day on days 1 and 2 and once on day 3 with a wash-out period of 6 days between the two periods. GFR was assessed using both measurement of creatinine clearance and calculation of inulin clearance and RPF was assessed using calculation of para-aminohippurate (PAH) clearance after the short-term administration on day 3. Urinary excretion of prostanoids (PGE(2), PGE-M, 6-keto-PGF(1alpha), 2,3-dinor-6-keto-PGF(1alpha), TxB(2), 2,3-dinor-TxB(2) and 11-dehydro-TxB(2)) were measured before and after drug intake.


RESULTS
Comparison with placebo showed no effect of diclofenac-colestyramine on creatinine, inulin or PAH clearance ( P>0.05) in patients with type-2 diabetes either without or with impaired renal function. The differences in creatinine, inulin and PAH clearance between the two groups of patients were not influenced by diclofenac-colestyramine. Urinary excretion of PGE(2), PGE-M, 6-keto-PGF(1alpha), 2,3-dinor-6-keto-PGF(1alpha), TxB(2), 2,3-dinor-TxB(2) ( P=1.89) and 11-dehydro-TxB(2) was significantly reduced by diclofenac-colestyramine.


CONCLUSIONS
These results indicate that proven non-specific cyclooxygenase inhibition by short-term administration of diclofenac-colestyramine did not affect renal haemodynamic function (GFR, RPF) in patients with type-2 diabetes either without or with impaired renal function.
Farker
K
K
Institute of Clinical Pharmacology, Friedrich Schiller University Jena, Dornburger Strasse 159, 07740 Jena, Germany. katrin.farker@med.uni-jena.de
Merkel
U
U
Schweer
H
H
Haerting
J
J
Madani
S F
SF
Eggers
R
R
Müller
U A
UA
Seyberth
H W
HW
Hoffmann
A
A
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D002792:Cholestyramine Resin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004008:Diclofenac / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011453:Prostaglandins / Q000652:urine*; D012079:Renal Circulation / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D011453:Prostaglandins; D002792:Cholestyramine Resin; D004008:Diclofenac