Pharmacokinetics of the thromboxane A2 receptor antagonist sulotroban (BM 13.177) in renal failure.
1. Ten healthy volunteers and 26 hospital in-patients with endogenous creatinine clearances of 98 to 4 ml min-1 received an oral dose of 800 mg sulotroban (BM 13.177). The plasma and urine concentrations of sulotroban were measured by gas-chromatography over 72 h and the pharmacokinetic parameters were calculated. 2. The AUC rose from 28.5 mg l-1 h in healthy volunteers to 631.4 mg l-1 h in preterminal renal failure (medians). The CLR decreased from 317.0 ml min-1 to 6.5 ml min-1 at the lowest renal capacity. 3. According to the AUC values, reduction of the dose is not necessary at CLCr greater than 50 ml min-1, a dose of 20-40% of normal is appropriate at CLCr of 20-50 ml min-1 At CLCr less than or equal to 20 ml min-1 the normal dose should be reduced to less than 20% of normal. 4. Vaginal spotting was noted in three female patients and a gastro-intestinal haemorrhage that did not require transfusion in one male patient. These may be associated with the action of sulotroban.
Piper
C
C
Medizinische Klinik A. Klinikum der Landeshauptstadt Wiesbaden, FRG.
Staiger
C
C
Jumeau-Ziemendorff
Y
Y
Uebis
V
V
Kaufmann
B
B
Stein
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003404:Creatinine / Q000097:blood; D005260:Female; D006207:Half-Life; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D017482:Receptors, Thromboxane; D013449:Sulfonamides / Q000493:pharmacokinetics
D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; C040624:sulotroban; D003404:Creatinine