Doripenem Dosing Recommendations for Critically Ill Patients Receiving Continuous Renal Replacement Therapy

Table 3

Probability of pharmacokinetic/pharmacodynamic target (fT > MIC ≥ 35%) attainment by CVVHDF flow rate in acute kidney impairment subjects.

MIC (mg/L)	CVVHDF flow rate (L/hr)
	1.25	1.75	2.25	2.5	2.75	3.25	3.5	3.75	4.5
Anephric subjects^a (250 mg q12h, 4-hour infusion)
1	0.985	0.981	0.978	0.975	0.973	0.968	0.966	0.963	0.954
2	0.578	0.547	0.514	0.500	0.482	0.452	0.439	0.424	0.379
4	0.017	0.014	0.011	0.010	0.009	0.008	0.006	0.006	0.005
8	0.000	0.000	0.000	0.000	0.000	0.000	0.000	0.000	0.000
Subjects with residual kidney function^b (500 mg q12h, 4-hour infusion)
1	0.999	0.999	0.999	0.998	0.998	0.998	0.998	0.998	0.998
2	0.952	0.944	0.937	0.933	0.929	0.919	0.914	0.911	0.896
4	0.367	0.345	0.323	0.311	0.3	0.279	0.269	0.259	0.231
8	0.005	0.003	0.003	0.002	0.002	0.002	0.002	0.001	0.001

aPharmacokinetic/pharmacodynamic target attainment probabilities for CVVHDF are based on a simulation of 5000 anephric subjects using mean pharmacokinetic parameter estimates from Cirillo et al. [14] with inflated between-subject variability (40% CV) and assuming a protein binding of 8.5%. Total CL represented the sum of 2 × CL_NR and CVVHDF clearance.
bThe renal component of the clearance allowed residual kidney function with a CrCL of 30 mL/min.