TABLE 1.
Bumetanide brain levels measured after peripheral doses administered to rodents.
| Compound | Dose | Species | Age/sex | Health status | Time of sacrifice after drug admin | Average brain levels | % Plasma drug reaching brain (brain to plasma ratio x100) | NKCC1 inhibitory levels of 100–300 nM a of bumetanide reached? | References | |
|---|---|---|---|---|---|---|---|---|---|---|
| Bumetanide | 0.15 mg/kg i.p | Rat | P10/male | Normal | 0.5 h | 0.51 ng/g (1.4 nM) [at 10 min 0.76 ng/g (2.11 nM)] | 0.43% | No | Cleary et al. (2013) | |
| Bumetanide | 0.15 mg/kg i.p | Rat | P10/male | 15 min after hypoxia/neonatal seizures | 0.5 h | 0.68 ng/g (1.8 nM) | 0.5% | No | Cleary et al. (2013) | |
| Bumetanide | 0.3 mg/kg i.p | Rat | P10/male | Normal | 0.5 h | 0.94 ng/g (2.6 nM) [at 10 min 1.2 ng/g (3.4 nM)] | 0.55% | No | Cleary et al. (2013) | |
| Bumetanide | 0.3 mg/kg i.p | Rat | P10/male | 15 min after hypoxia/neonatal seizure | 0.5 h | 1.07 ng/g (27 nM) | 0.5 | No | Cleary et al. (2013) | |
| Bumetanide | 0.3 mg/kg i.p | Rat | P11/both sexes | ∼10 min after asphyxia/neonatal seizures | ∼1 h | 10 ng/g (27 nM) | 3.6% | No | Johne et al. (2021b) | |
| Bumetanide | 0.3 mg/kg i.p | Rat | Adult/male | Normal | 0.5 h | ∼1.4 ng/g (3.8 nM) | 0.68% | No | Li et al. (2011) | |
| Bumetanide | 0.5 mg/kg i.p daily for 3 weeks | Rat | P10/both sexes | Normal | 0.5 h after last drug injection | 1.7 ng/g (4.7 nM) | 0.46% | No | Wang et al. (2015) | |
| Bumetanide | 0.5 mg/kg i.p daily for 3 weeks | Rat | P10/both sexes | Hypoxia/neonateseizures | 0.5 h after last drug injection | 2.2 ng/g (6 nM) | 0.77% | No | Wang et al. (2015) | |
| Bumetanide | 2 mg/kg i.v | Mouse | Adult | Normal | 5 min (Cmax) | ∼60 ng/g (160 nM) | ∼0.5% | Yes | Savardi et al. (2020) | |
| Bumetanide | 10 mg/kg i.v | Rat | Adult/female | Normal | 0.25 h (Cmax) | 53 ng/g (150 nM) (cortex and amygdala) | 1.4% | Yes | Töllner et al. (2015) | |
| Bumetanide | 10 mg/kg i.v | Rat | Adult/female | Normal | 0.25 h (Cmax) | 11.8 ng/g (320 nM) (cortex and amygdala) | 1.4% | Yes | Tôpfer et al. (2014) | |
| Bumetanide | 10 mg/kg i.v, then i.v. with 6 mg/kg/h over 5 h | Rat | Adult/male | Normal | Hippocampal dialysate, drug measured after 5-h drug infusion | 1,370 ng/g (3,760 nM) hippocampus; 132 ng/mL (360 nM) in dialysate | ∼6% for whole tissue but only ∼0.01% for dialysate (extracellular) levels | Yes (also in the extracellular fluid) | Donovan et al. (2015) | |
| Bumetanide | 10 mg/kg i.v | Mouse | Adult/female | Normal | 0.5 h | 330 ng/g (910 nM) | 1.6% | Yes | Töllner et al. (2015) | |
| Bumetanide | 10 mg/kg i.v | Mouse | Adult/female | Normal | 0.5 h | 270 ng/g (740 nM) | 1.8% | Yes | Töllner et al. (2015) | |
| Bumetanide | 10 mg/kg i.v | Mouse | Adult/female | Normal | 0.25 h | 380 ng/g (1,040 nM) | 1.1% | Yes | Römermman et al. (2017) | |
| Bumetanide | 10 mg/kg i.v | Mouse | Adult/female | Normal | 2 min (Cmax) | 1,030 ng/g (2,830 nM) | 1.5% | Yes | Hampel et al. (2021) | |
| Bumetanide | 10 mg/kg i.v | Rat | P11/both sexes | ∼10 min after asphyxia/neonatal seizures | ∼1 h | 190 ng/g (520 nM) | 2.5% | Yes | Johne et al. (2021a) | |
a
Bumetanide at 100–300 nM has been reported to represent the minimal concentrations to inhibit NKCC1 (Löscher and Kaila, 2022). It is noted that the reported IC50 values of bumetanide have variability from study to study (Hampel et al., 2018; Löscher and Kaila, 2022).