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.