Pharmacokinetics of the thromboxane A2 receptor antagonist sulotroban (BM 13.177) in renal failure.

Abstract

1 Ten healthy volunteers and 26 hospital in-patients with endogenous creatinine clearances of 98 to 4 ml min-' 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 1-1 h in healthy volunteers to 631.4 mg 1-1 h in preterminal renal failure (medians). The CLR decreased from 317.0 ml min-' 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 > 50 ml min-', a dose of 20-40% of normal is appropriate at CLCr of 20-50 ml min-'. At CLCr ' 20 ml min-' the normal dose should be reduced to < 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.

Sulotroban (BM 13.177)

“…The pharmacokinetics of sulotroban has been examined in patients with varying degrees of chronic renal failure (32). These data are summarized in Table 2.…”