Effect of chronic pentobarbital treatment on blood-cerebrospinal fluid kinetics

Okamoto, Michiko; Boisse, N R

doi:10.1016/0014-2999(75)90159-4

Cited by 10 publications

(3 citation statements)

References 4 publications

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“…Such models do not directly estimate the concentration of the medication in the CNS, its site of action (17,18). Animal models, however, suggest that both midazolam and pentobarbital rapidly distribute into the CNS from serum, suggesting that our models may be sufficient for estimating their CNS concentration (19,20).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Modeling of Optimized Midazolam and Pentobarbital Dosing Used in Treatment Protocols of Refractory Status Epilepticus

Luchette

LaRovere

et al. 2022

Pediatric Critical Care Medicine

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To model bolus dosing, infusion rate, and weaning rate on theoretical serum concentration of midazolam and pentobarbital used in the treatment of refractory status epilepticus (RSE). DESIGN:One-and two-compartment in silico pharmacokinetic models of midazolam and pentobarbital. SETTING: Not applicable. SUBJECTS: Not applicable. INTERVENTIONS:We compared the model variables used in midazolam and pentobarbital protocols for standard RSE. MEASUREMENTS AND MAIN RESULTS:Standard RSE treatment protocols result in steady-state serum concentrations that are 6.2-9.0-fold higher for the one-compartment model and 2.3-4.7-fold higher for the two-compartment model. In the model, not including bolus doses delays the achievement of serum steady-state concentration by 0.5 and 2.7 hours for midazolam and pentobarbital, respectively. Abrupt discontinuation of these medications reduces modeled medication exposure by 1.1 and 6.4 hours, respectively. CONCLUSIONS:Our in silico pharmacokinetic modeling of standard midazolam and pentobarbital dosing protocols for RSE suggests potential variables to optimize in future clinical studies.

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Section: Discussionmentioning

confidence: 99%

Pharmacokinetic Modeling of Optimized Midazolam and Pentobarbital Dosing Used in Treatment Protocols of Refractory Status Epilepticus

Luchette

LaRovere

et al. 2022

Pediatric Critical Care Medicine

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“…One other possibility to explain our findings in the SE-BS group could be related to a differential effect of pentobarbital at varying brain concentrations, with a more uniform action at low brain concentrations and greater variability at higher levels. Chronic infusion of pentobarbital in cats produced stable CSF pentobarbital levels, which varied proportionately with serum levels (Okamoto and Boisse 1975). Furthermore, it was found that the CSF pentobarbital half-life was the same as the serum half-life (Okamoto and Boisse 1975).…”

Section: Although the Eeg Pattern Of Bs Is Characteristic There Are mentioning

confidence: 90%

“…Chronic infusion of pentobarbital in cats produced stable CSF pentobarbital levels, which varied proportionately with serum levels (Okamoto and Boisse 1975). Furthermore, it was found that the CSF pentobarbital half-life was the same as the serum half-life (Okamoto and Boisse 1975). These findings would make fluctuations in serum or brain concentration an unlikely explanation for IBI variability.…”

Section: Although the Eeg Pattern Of Bs Is Characteristic There Are mentioning

confidence: 92%

Variance of interburst intervals in burst suppression

Beydoun

Yen

Drury

1991

Electroencephalography and Clinical Neurophysiology

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Each EEG performed over a 3 year period at the University of Michigan with a diagnosis of generalized burst-suppression (BS) was reviewed. Ten EEGs from 10 patients with hypoxic-ischemic encephalopathy (HIE-BS) and 21 records from 8 patients with pentobarbital induced burst-suppression for treatment of status epilepticus (SE-BS) were reviewed. For each EEG, the mean duration of 40 interburst intervals (IBIs) as well as their coefficient of variability were calculated. We found that in the SE-BS group the coefficient of variability of IBI duration was highly correlated with the logarithm of mean IBI duration while in the HIE-BS group, there was no significant correlation between these 2 variables. This suggests that the underlying mechanism causing BS is different in the 2 groups and might be related to a uniform and progressive affection of similar brain structures in the SE-BS group and a more patchy and variable pathology in the HIE-BS group.

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