Table 3.
PK/TD parameters estimates following intraperitoneal administration of CMS and CMS-E2.
| Drug | PK | |||||
|---|---|---|---|---|---|---|
| Dose (mg·kg CBA) | Ka CMS/CMS−E2(1/h) | CLCMS/CMS−E2 (mL/min/kg) | CLcolistin/colistin B (mL/min/kg) | V (mL/kg) | KCMS, colistin/KCMS−E2, colistin B (mL/min/kg) | |
| CMS | 10 | 2.02 ± 0.260 | 5.14 ± 0.196 | 2.57 ± 0.420 | 194 ± 12.8 | 0.756 ± 0.0208 |
| 20 | 0.878 ± 0.342 | 2.52 ± 1.64 | 1.75 ± 1.21 | 199 ± 84.6 | 1.21 ± 0.381 | |
| CMS-E2 | 20 | 1.20 ± 0.253 | 9.69 ± 3.95 | 3.31 ± 1.03 | 263 ± 58.3 | 1.40 ± 0.125 |
| 40 | 0.673 ± 0.208 | 3.20 ± 1.74 | 1.89 ± 0.809 | 291 ± 105 | 1.46 ± 0.124 | |
| TD | ||||||
|---|---|---|---|---|---|---|
| Drug | Ke (1/h) | Tlag (h) | E0 (CR: µmol/L, BUN: mmol/L) | S (CR: mmol/g, BUN: mol/g) | ||
| CR | CMS | 0.833 ± 0.555 | 1.73 ± 1.22 | 24.2 ± 3.65 | 20.9 ± 9.13 | |
| CMS-E2 | 0.814 ± 0.524 | 1.83 ± 1.05 | 23.0 ± 4.63 | 13.0 ± 3.52 | ||
| BUN | CMS | 0.157 ± 0.100 | 8.45 ± 4.08 | 4.54 ± 0.841 | 11.7 ± 7.27 | |
| CMS-E2 | 0.182 ± 0.164 | 11.9 ± 9.46 | 4.01 ± 0.789 | 7.78 ± 4.56 | ||
CMS colistin methanesulphonate, CMS-E2 colistin B methanesulphonate, CBA colistin base activity, Ka CMS/CMS−E2, absorption rate of CMS/CMS-E2; CLCMS/CLCMS−E2, total body clearance of CMS/CMS-E2; CLcolistin/CLcolistin B, total body clearance of colistin/colistin B; V, volume of distribution; KCMS, colistin/KCMS−E2, colistin B, metabolic rate from CMS/CMS-E2 compartment to colistin/colistin B compartment; Ke, elimination rate from colistin/colistin B central compartment to effect compartment; Tlag, lag time; E0, baseline level of blood creatinine and urea nitrogen prior to drug administration; S, proportional coefficient between the drug concentrations and the effect; CR creatinine, BUN blood urea nitrogen.