Novel application of acetazolamide to reduce cerebrospinal fluid production in patients undergoing thoracoabdominal aortic surgery

Jafarzadeh, Fatemeh; Field, Mark; Harrington, Deborah; Kuduvalli, Manoj; Oo, Aung; Kendall, John; Desmond, M. Sheila; Mills, Keith

doi:10.1093/icvts/ivt384

Cited by 14 publications

(9 citation statements)

References 7 publications

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“…The CSF turnover rate sets the efficiency of convective clearance out of the CNS. It is well documented that CSF production rates vary under different conditions, including circadian rhythm [ 33 – 36 ], normal aging [ 36 – 39 ], concurrent medications such as the carbonic anhydrase inhibitor acetazolamide [ 40 , 41 ] and the proton pump inhibitor omeprazole [ 42 , 43 ], and in disease conditions such as hydrocephalus [ 26 , 44 ] and Alzheimer’s disease (AD) [ 45 , 46 ]. Alterations in CSF production rates can have profound effects on CNS clearance of medications and waste products.…”

Section: Discussionmentioning

confidence: 99%

Monoclonal antibody exposure in rat and cynomolgus monkey cerebrospinal fluid following systemic administration

Wang

Delva

Weinreb

et al. 2018

Fluids Barriers CNS

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BackgroundMany studies have focused on the challenges of small molecule uptake across the blood–brain barrier, whereas few in-depth studies have assessed the challenges with the uptake of antibodies into the central nervous system (CNS). In drug development, cerebrospinal fluid (CSF) sampling is routinely used as a surrogate for assessing CNS drug exposure and biomarker levels. In this report, we have studied the kinetic correlation between CSF and serum drug concentration–time profiles for five humanized monoclonal antibodies in rats and cynomolgus monkeys and analyzed factors that affect their CSF exposure.ResultsUpon intravenous (IV) bolus injection, antibodies entered the CNS slowly and reached maximum CSF concentration (CSFTmax) in one to several days in both rats and monkeys. Antibody serum and CSF concentration–time curves converged until they became parallel after CSFTmax was reached. Antibody half-lives in CSF (CSFt½) approximated their serum half-lives (serumt½). Although the intended targets of these antibodies were different, the steady-state CSF to serum concentration ratios were similar at 0.1–0.2% in both species. Independent of antibody target and serum concentration, CSF-to-serum concentration ratios for individual monkeys ranged by up to tenfold from 0.03 to 0.3%.ConclusionUpon systemic administration, average antibodies CSF-to-serum concentration ratios in rats and monkeys were 0.1–0.2%. The CSFt½ of the antibodies was largely determined by their long systemic t½ (systemict½).

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Section: Discussionmentioning

confidence: 99%

Monoclonal antibody exposure in rat and cynomolgus monkey cerebrospinal fluid following systemic administration

Wang

Delva

Weinreb

et al. 2018

Fluids Barriers CNS

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“…There are many CAs inhibitors, such as sulfonamide, phenols, coumarins, dithiocarbamates, benzamides, and mercaptans that have been tested against β-CAs to control many infectious organisms (Syrjänen et al 2013). Acetazolamide is a sulfonamide (de Sousa et al 2012) and acts as carbonic anhydrase inhibitor that is used for the medical treatment of epileptic seizures, idiopathic intracranial hypertension, and altitude sickness (Jafarzadeh et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Carbonic anhydrase enzyme as a potential therapeutic target for experimental trichinellosis

et al. 2016

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Trichinellosis is a globally distributed helminthic infection. There is a considerable interest in developing new anti-helminthic drugs affecting all the developmental stages of Trichinella. Acetazolamide (carbonic anhydrase (CA) inhibitor) involves a novel mechanism of action by inhibiting such an essential enzyme for parasite metabolism. This work aimed to study the effect of acetazolamide against different stages of T. spiralis in experimental animals. Mice were divided into three groups: group I: infected and treated with acetazolamide on day 2 post infection (P.I.), group II: infected and treated with acetazolamide on day 12 P.I., and group III: infected non-treated. From each group, small intestine and muscles were removed for histopathological and immunohistochemical studies. Also, total adult and muscle larval count were estimated. We found that acetazolamide was effective in reduction of both adult and muscle larval counts. When given early, the effect was more pronounced on the adults (62.7 %). However, the efficacy of the drug against muscle larvae was increased when given late (63 %). Improvement of the intestinal histopathological changes was observed in all the treated groups. Degeneration of encysted larvae with minimal pathologic changes of infected skeletal muscle was observed in the treated groups. Expression of matrix metalloproteinase-9 showed a statistically significant decrease in the intestinal and muscle tissues in all treated groups as compared to the control group. In conclusion, the present study revealed that acetazolamide, carbonic anhydrase inhibitor, could be a promising drug against both adults and larvae of T. spiralis.

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“…20 Others have described acetazolamide reducing CSF production after TAAAR, which seems reasonable for treating delayed SCD. 21 Paraplegia lasting beyond 24 to 48 hours is probably permanent.…”

Section: Postoperative Considerations Neurologicmentioning

confidence: 99%

Perioperative care after thoracoabdominal aortic aneurysm repair: The Baylor College of Medicine experience. Part 2: Postoperative management

Chatterjee

Casar

LeMaire

et al. 2021

The Journal of Thoracic and Cardiovascular Surgery

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Novel application of acetazolamide to reduce cerebrospinal fluid production in patients undergoing thoracoabdominal aortic surgery

Cited by 14 publications

References 7 publications

Monoclonal antibody exposure in rat and cynomolgus monkey cerebrospinal fluid following systemic administration

Monoclonal antibody exposure in rat and cynomolgus monkey cerebrospinal fluid following systemic administration

Carbonic anhydrase enzyme as a potential therapeutic target for experimental trichinellosis

Perioperative care after thoracoabdominal aortic aneurysm repair: The Baylor College of Medicine experience. Part 2: Postoperative management

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