Mannitol and the blood-labyrinth barrier

Table 2 Pharmacokinetic Parameters of Gentamicin Concentrations in CSF

Parameter	Gentamicin(ng/ml) given alone in CSF(95%CI)	Gentamicin(ng/ml) with mannitol in CSF(95%CI)
Y_max	79 (50–100)	66 (52–80)
k₁	0.65 (−0.25–1.3)	4.5 (−4.3–13)
k₂	0.11 (−0.026–0.25)	0.12 (−0.014–0.24)
R ²	0.32	0.36

Data were fit to the sum of two first-order exponential equations and meant to model the sum of absorption and elimination of gentamicin from CSF. The overall equation is eq. 2, [\( y(t)={y}_{max}\left[{e}^{-{k}_1t}+\left(1-{e}^{-{k}_{2^{\left(t-4\right)}}}\right)\right] \) where k₁ and k₂ parameters are rate constants for decrease and increase concentration (hours⁻¹), respectively, which determine the overall rate of change of the concentration for gentamicin. Y_max is the maximum gentamicin concentration (ng/ml) and y(t) is the concentration of gentamicin at time t (hours). Fitted parameters for eq. 2, (for +/− 95% confidence interval), were y_max = 79 (+/− 50–100) ng/ml; k₁ = 0.65 (+/− −0.25-1.3) hrs⁻¹; k₂ = 0.11(+/− −0.026-0.25) hrs⁻¹. Parameterized eq. 2 is therefore: [y(t) = 79[e ^−0.65t + (1 − e ^{−0.11(t − 4)})]. The half lives for decrease and increase were 1.07 and 6.3 h respectively. R² was 0.32, indicating that 32% of the variability was accounted for by the model. This amount seems somewhat low, probably due to the difficulty in fitting the phase of increasing concentration. These data suggest that mannitol does not significantly change the permeability of the blood-brain barrier to gentamicin

ISSN: 1916-0216