TABLE 5

Clinically observed and PBPK model-predicted pharmacokinetic parameters of bosutinib in subjects with renal impairment after a single oral administration of 200 mg bosutinib

Data are expressed as geometric means with percent coefficients of variation in parentheses or as median tmax values with ranges in parentheses.

PopulationAnalysisPK ParameterRatioa
CmaxtmaxAUCCmaxRAUCR
ng/mlhng⋅h/ml
HVsObserved33 (46)5.0 (2.0–6.0)993 (37)
Predicted30 (43)5.2 (3.0–7.8)944 (53)
P/O0.91.0
Moderate RIPsObserved42 (23)5.0 (3.0–12)1404 (44)1.31.4
Predicted41 (49)6.0 (3.8–10)1566 (55)1.41.7
P/O1.01.11.11.2
Severe RIPsObserved44 (30)6.0 (3.0–12)1575 (34)1.31.6
Predicted42 (48)6.0 (4.0–11)1611 (54)1.41.7
P/O1.01.01.11.1
  • Dashes indicate not applicable.

  • a Ratios of Cmax and AUC in RIPs to HVs.