TABLE 1.

Final population PK model for ceftaroline fosamil^a

Parameterb	Estimate	% SEM
CLp (liters/h)c	228	2.59
CLp-CLCR power	0.147	26.5
Vc,p (liters)d	10.8	8.35
Vc,p shift for SEVj	17.2	32.8
Vc,p shift for POPj	−5.81	18.8
CLd1p (liters/h)	25.7	11.3
Vp1 (liters)	363	15.2
CLd2p (liters/h)	16.2	11.8
Vp2 (liters)	3.24	6.00
F	1.23	4.96
ka (h−1)	0.627	8.12
FRC	0.772	5.73
tlag (h)	0.462	7.36
ω2ka	26.4% CVe	50.7
ω2CLp	25.7% CV	13.2
ω2Vc,p	68.2% CV	13.5
ω2CLd1p	70.3% CV	24.4
σ2 for studies 1, 2, and 3	34.2% CV	4.91
σ2 for all other studies	36.6% CV	5.80

^aData were obtained from reference 8.

^bCL_d1p, prodrug distribution clearance for the first peripheral compartment; CL_d2p, prodrug distribution clearance for the second peripheral compartment; CL_p, prodrug clearance; F, intramuscular bioavailability; FRC, fraction of prodrug dose in the first depot compartment; k_a, first-order absorption rate constant; ω², interindividual variability; σ², residual variability; t_lag, delay in the start of absorption from the second depot compartment; V_c,p, prodrug central volume of distribution; V_p1, prodrug volume of distribution for the first peripheral compartment; V_p2, prodrug volume of distribution for the second peripheral compartment.

^cPopulation mean CL_p (liters/h) = 228 · (CL_CRj/102)^0.147.

^dPopulation mean V_c,p (liters/h) = 10.8 + 17.2 · SEV_j − 5.81 · POP_j, where SEV_j is an indicator variable in the jth subject with a value of 1 if CL_CR < 30 ml/min/1.73 m² and 0 otherwise and POP_j is an indicator variable in the jth subject with a value of 1 for phase 2/3 patients and 0 otherwise.

^eCV, coefficient of variation.