Cerebrospinal Fluid and Plasma Pharmacokinetics of Phenobarbital after Intravenous Administration to Patients with Status Epilepticus

Brzaković, Branka; Pokrajac, M.; Džoljić, Eleonora; Lević, Z; Varagić, V.M.

doi:10.2165/00044011-199714040-00009

Cited by 5 publications

(2 citation statements)

References 10 publications

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“…The CSF/serum ratio for G6 dendrimers ranged from 0.02–0.20 (on average) during the entire monitoring period, which is close to several common neuroactive agents (leptin, morphine, phenobarbital) after repetitively dosed to patients on daily bases [25, 26, 27]. When evaluating area under the curve (AUC) to determine the profile of CSF/serum ratios over time, the AUC of G6 dendrimers is also higher than several clinically used antibiotics, such as penicillin, cloxacillin, amoxicillin, piperacillin, clavulanatem, and cephalosporins (data not shown) [28].…”

Section: Resultsmentioning

confidence: 99%

Generation-6 hydroxyl PAMAM dendrimers improve CNS penetration from intravenous administration in a large animal brain injury model

Zhang

Magruder

Lin³

et al. 2017

Journal of Controlled Release

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Hypothermic circulatory arrest (HCA) provides neuroprotection during cardiac surgery but entails an ischemic period that can lead to excitotoxicity, neuroinflammation, and subsequent neurologic injury. Hydroxyl polyamidoamine (PAMAM) dendrimers target activated microglia and damaged neurons in the injured brain, and deliver therapeutics in small and large animal models. We investigated the effect of dendrimer size on brain uptake and explored the pharmacokinetics in a clinically-relevant canine model of HCA-induced brain injury. Generation 6 (G6, ~6.7 nm) dendrimers showed extended blood circulation times and increased accumulation in the injured brain compared to generation 4 dendrimers (G4, ~4.3 nm), which were undetectable in the brain by 48 hrs after final administration. High levels of G6 dendrimers were found in cerebrospinal fluid (CSF) of injured animals with a CSF/serum ratio of ~20% at peak, a ratio higher than that of many neurologic pharmacotherapies already in clinical use. brain penetration (measured by drug CSF/serum level) of G6 dendrimers correlated with the severity of neuroinflammation observed. G6 dendrimers also showed decreased renal clearance rate, slightly increased liver and spleen uptake compared to G4 dendrimers. These results, in a large animal model, may offer insights into the potential clinical translation of dendrimers.

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Section: Resultsmentioning

confidence: 99%

Generation-6 hydroxyl PAMAM dendrimers improve CNS penetration from intravenous administration in a large animal brain injury model

Zhang

Magruder

Lin³

et al. 2017

Journal of Controlled Release

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“…The inter- and intraday relative standard deviations of lamotrigine assays using HPLC reported in a different study were lower than 15% for all measured analytes while for valproic acid, the assay using GC had a coefficient of variation (C.V.) lower than 4% ( Wang et al , 2015b ). One study reported the inter- and intraday CV for lamotrigine assayed using HPLC as 6.57 ± 2.01% and 4.95 ± 1.87% precision ( Brzaković et al , 2012 ) while another reported similar CV being less than 8% and less than 12% respectively, for phenobarbital in both cerebrospinal fluid and plasma assayed using reversed-phase HPLC-UV ( Brzaković et al , 1997 ). In terms of quality control, duplicate determinations were the most commonly used quality control methods and were reported in four (28%) of these studies, two studies on lamotrigine and two on phenytoin.…”

Section: Resultsmentioning

confidence: 99%

Therapeutic monitoring of anti-seizure medications in low- and middle-income countries: a systematic review

Odhiambo,

Kariuki,

Newton

2024

Wellcome Open Res

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Background The treatment gap for epilepsy is large in low- and middle-income countries (LMICs) and the effectiveness and safety of the available anti-seizure medication (ASMs) is not fully understood. We systematically reviewed available evidence on therapeutic drug monitoring (TDM) of ASM in LMIC. Methods We searched four main databases (PubMed, Psych-Info, CINAHL and Embase) up to 31st December 2020, with eligible articles screened using a PRISMA checklist and a set of exclusion and inclusion criteria. Full texts were examined to evaluate the extent and practice of TDM in LMICs. Analyses were performed using Stata 13 and descriptive statistics were used to pool median distribution of TDM across studies. Results Of the 6,309 articles identified in the initial search, 65 (1.0%) met the eligibility criteria. TDM of ASMs was mostly done to assess toxicity (42.8%), but rarely to monitor adherence (9.0%). TDM differed by economic status and infrastructural status with majority of the studies coming from Europe (53.8%) and upper-middle-income countries (87.6%). First generation ASMs (82.3%) were more likely to be monitored than second generation ASMs (17.6%) and carbamazepine was the most frequently monitored drug. Fluorescence Polarization Immunoassay (FPIA) was the most common technique used for TDM (41.5%) followed by High-Performance Liquid Chromatography (HPLC) (16.9%). In addition, FPIA was the cheapest method of TDM based on approximated costs ($1000, TDx system). Assay validation and quality control were reported variably, and reference ranges used during TDM of ASMs were relatively uniform. Conclusions TDM is mostly done to evaluate ASM toxicity, but rarely for other reasons such as evaluating adherence or assessing clinical efficacy. There is a need for more investment in comprehensive and targeted TDM in LMICs when initiating treatment, switching therapies, adding or removing ASM and evaluating treatment response and safety of both first generation and second generation ASMs.

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Effect of phenobarbital on seizure frequency and mortality in childhood cerebral malaria: a randomised, controlled intervention study

et al. 2000

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Cerebrospinal Fluid and Plasma Pharmacokinetics of Phenobarbital after Intravenous Administration to Patients with Status Epilepticus

Cited by 5 publications

References 10 publications

Generation-6 hydroxyl PAMAM dendrimers improve CNS penetration from intravenous administration in a large animal brain injury model

Generation-6 hydroxyl PAMAM dendrimers improve CNS penetration from intravenous administration in a large animal brain injury model

Therapeutic monitoring of anti-seizure medications in low- and middle-income countries: a systematic review

Effect of phenobarbital on seizure frequency and mortality in childhood cerebral malaria: a randomised, controlled intervention study

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