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. 2014 Feb;58(2):1005–1018. doi: 10.1128/AAC.00350-13

TABLE 3.

Primary pharmacodynamics parameters and mathematical quality of respective nonlinear regressions obtained from the dose-response relationships of the different animal modelsa

Bacterial pathogen Model M:C ratio Meropenem formb Emax (mean Δlog10 CFU/g at 24 h ± SEM) BD (mean mg/kg/day ± SEM) N (mean Hill's slope ± SEM) PDP with multicollinearity P value (CFA) T>MIC for BD (%)
P. aeruginosa GRP-0019 Mouse thigh 1:0 iMer NSc NS 0.769 ± 0.287 All NAd NA
gMer-B NS NS 0.673 ± 0.242 All
gMer-C NS NS 0.645 ± 0.252 All
P. aeruginosa GRP-0019 Mouse thigh 1:0 iMer 6.358 ± 0.202 105.50 ± 8.07 2.079 ± 0.297 None 0.3220 67.9
gMer-A 6.028 ± 0.160 121.20 ± 7.36 2.948 ± 0.463 None 76.3
P. aeruginosa GRP-0019 Mouse thigh 1:1 iMer 5.929 ± 0.267 33.26 ± 2.53 3.025 ± 0.713 None 0.4150 19.5
gMer-A 6.480 ± 0.267 37.65 ± 2.34 2.243 ± 0.351 None 21.3
P. aeruginosa GRP-0019 Mouse thigh 1:3 iMer 6.935 ± 0.196 44.57 ± 2.32 1.861 ± 0.199 None 0.2310 23.8
gMer-A 7.019 ± 0.236 47.12 ± 2.55 1.520 ± 0.158 None 24.7
P. aeruginosa GRP-0049 Mouse thigh 1:1 iMer 6.836 ± 0.532 85.74 ± 5.17 1.303 ± 0.166 Emax, BD NA NA
gMer-A 6.465 ± 0.187 62.62 ± 2.31 1.857 ± 0.154 None 18.7
P. aeruginosa GRP-0049 Mouse thigh 1:3 iMer 5.827 ± 0.164 60.60 ± 3.03 3.290 ± 0.472 None 0.9863 18.2
gMer-A 5.797 ± 0.151 59.65 ± 2.79 3.529 ± 0.480 None 18.0
P. aeruginosa GRP-0049 Mouse thigh 1:5 iMer 5.812 ± 0.187 54.66 ± 3.22 3.102 ± 0.502 None 0.9661 16.8
gMer-A 5.904 ± 0.177 54.47 ± 2.98 3.225 ± 0.493 None 16.8
P. aeruginosa GRP-0019 Mouse brain 1:0 iMer 6.482 ± 0.212 66.25 ± 7.19 1.444 ± 0.236 None 0.0020 31.5
gMer-B 6.931 ± 0.295 58.88 ± 7.56 1.167 ± 0.235 None 28.7
gMer-C 5.900 ± 0.104 44.29 ± 3.35 3.140 ± 0.415 None 23.7
P. aeruginosa GRP-0019 Mouse brain 1:0 iMer 6.427 ± 0.520 41.07 ± 4.07 0.689 ± 0.179 All NA NA
gMer-A 5.916 ± 0.318 44.03 ± 5.15 1.115 ± 0.279 Emax, BD NA
P. aeruginosa GRP-0019 Mouse brain 1:1 iMer 7.164 ± 0.207 50.21 ± 2.81 0.846 ± 0.105 None NA 25.7
gMer-A 6.605 ± 0.167 60.73 ± 4.37 1.279 ± 0.173 Emax, N NA
P. aeruginosa GRP-0019 Mouse brain 1:3 iMer 6.537 ± 0.168 81.94 ± 6.86 2.057 ± 0.245 None <0.0001 41.5
gMer-A 7.279 ± 0.167 120.20 ± 5.80 1.709 ± 0.125 None 75.8
P. aeruginosa GRP-0049 Mouse brain 1:1 iMer 5.874 ± 0.2373 121.6 ± 10.7 3.676 ± 0.827 None NAe NA
gMer-A 6.311 ± 0.3355 96.11 ± 9.67 2.164 ± 0.4129 None 25.0
P. aeruginosa GRP-0049 Mouse brain 1:3 iMer 6.498 ± 0.113 87.64 ± 3.92 1.797 ± 0.126 None 0.0002 23.5
gMer-A 6.498 ± 0.363 136.80 ± 13.3 1.599 ± 0.246 None 32.4
K. pneumoniae GRP-0107 Mouse lung 1:0 iMer NS NS 0.722 ± 0.288 All NA NA
gMer-A NS NS 0.784 ± 0.259 All NA
K. pneumoniae GRP-0107 Mouse lung 1:0 iMer 5.577 ± 0.310 13.91 ± 2.46 0.843 ± 0.166 None 0.1265 (iMer vs gMer-B)f 92.9
gMer-B 5.764 ± 0.526 26.69 ± 6.10 0.771 ± 0.182 Emax, BD NA
gMer-C 5.906 ± 0.913 NS 0.614 ± 0.195 All NA
K. pneumoniae GRP-0107 Mouse lung 1:3 iMer 5.916 ± 0.614 5.37 ± 1.25 0.875 ± 0.386 Emax, N NA NA
gMer-A 6.774 ± 0.955 9.89 ± 1.37 0.780 ± 0.237 All NA
K. pneumoniae GRP-0107 Mouse lung 1:5 iMer 5.137 ± 0.260 9.05 ± 1.04 1.719 ± 0.453 None NA 85.0
gMer-A NS NS 0.395 ± 0.152 All NA
P. aeruginosa GRP-0019 Guinea pig soleus 1:0 iMer 6.485 ± 0.094 11.53 ± 0.40 3.331 ± 0.351 None <0.0001 NDg
gMer-A 6.642 ± 0.345 21.60 ± 2.55 1.444 ± 0.274 None ND
P. aeruginosa GRP-0019 Guinea pig soleus 1:0 iMer 6.463 ± 0.184 10.99 ± 1.10 1.438 ± 0.257 None <0.0001f ND
gMer-B 6.349 ± 0.162 11.75 ± 0.99 1.503 ± 0.239 None ND
gMer-C 7.238 ± 0.466 25.12 ± 2.84 1.082 ± 0.197 Emax ND
a

The ranges of the adjR2 and Sy|x were 0.7 to 0.988 and 0.222 to 0.624, respectively (data not shown).

b

gMer-A, generic product Vitalis; gMer-B, generic product Procaps; gMer-C, generic product Farmioni.

c

NS, not significant.

d

NA, not applicable. Statistical comparison of this regression was not possible due to serious multicollinearity of the PDP in one or both products.

e

*, in this instance in which this parameter was not applicable, violation of normality and homoscedasticity assumptions (iMer) prevented statistical comparison.

f

In this experiment, a formal statistical comparison was indicated because only one product had multicollinearity and it was mild (highest VIF, <7.0).

g

ND, not done.