Pharmacokinetic parameters for DPHM in plasma CSF and ECF (n = 6 in all cases, except for the ECF concentrations in the DPHM-PRN study, where n = 3) Data are shown as mean ± S.D.
DPHM (0–4 h) | DPHM-PRN (4–8 h) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Plasma | CSF | ECF | Plasma | CSF | ECF | |||||
| ClT (ml/min/kg) | 29.9 ± 9.6 | N.A. | N.A. | 36.7 ± 10.5 | N.A. | N.A. | ||||
| Vdss (l/kg) | 27.9 ± 17.4 | N.A. | N.A. | 22.5 ± 13.5 | N.A. | N.A. | ||||
| PB (%) | 83.0 ± 2.2 | N.A. | N.A. | 84.4 ± 10.5 | N.A. | N.A. | ||||
| f ratio | N.A. | 0.40 ± 0.20 | 0.40 ± 0.20 | N.A. | 0.69 ± 0.03* | 0.95 ± 0.05* | ||||
| t1/2β (h)a | 10.8 ± 5.4 | 3.6 ± 1.0 | 5.3 ± 4.2 | 7.2 ± 3.5 | 4.4 ± 3.4 | 8.3 ± 4.8 | ||||
| t1/2α (h)a | 0.5 ± 0.2 | 0.6 ± 0.2 | 0.5 ± 0.3 | 0.3 ± 0.2 | 0.6 ± 0.3 | 0.9 ± 0.2# | ||||
PB, extent of protein binding. N.A., data not available
↵ a Model-fitted parameters obtained from the two-compartment modeling of the five-step and DPHM-PRN coinfusions
↵* Significantly different from the respective DPHM value alone (unpaired t test)
↵# Significantly different from the respective five-step infusion value (paired t test)