Safety of carbonic anhydrase inhibitors

Swenson, Erik R.

doi:10.1517/14740338.2014.897328

Cited by 57 publications

(49 citation statements)

References 113 publications

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“…The other situation in which large differences between tissue and arterial blood pH and P CO 2 can occur is when acetazolamide or any other carbonic anhydrase inhibitor is given in doses (Ͼ500 mg or lesser doses when renal clearance of the drug is impaired) that lead to significant red cell carbonic anhydrase inhibition. 12 Under these circumstances, the normal capacity of blood to rapidly interconvert CO 2 and bicarbonate within the 0.5-1.0 s of capillary transit in the lungs and tissues disappears, and the ability to use bicarbonate as a transport form of CO 2 is lost. Unless one measures tissue P CO 2 or surrogates for it, such as central or mixed venous blood, the presence and magnitude of tissue CO 2 retention will go wholly unrecognized.…”

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confidence: 99%

Circumstances When Arterial Blood Gas Analysis Can Lead Us Astray

Albert

Swenson

2015

Respir Care

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confidence: 99%

Circumstances When Arterial Blood Gas Analysis Can Lead Us Astray

Albert

Swenson

2015

Respir Care

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“…These are side effects typical for the first-generation, nonselective CAIs, such as AAZ and MZA, and are due to the inhibition of the CA isoforms not involved in CSF formation [8][9][10][11]. However, as showed recently by Swenson, the sulfonamide CAIs show an impressive safety profile despite the multiple functions in which many CA isoforms are involved in many organs/tissues [44]. This is probably due to the residual activity of isoforms, which were not inhibited by the used drugs as well as the uncatalyzed rates of CO 2 hydration, in combination with compensations, which avoid lethal consequences for the use of these pharmacologic agents.…”

Section: Clinical Trialsmentioning

confidence: 99%

Acetazolamide for the treatment of idiopathic intracranial hypertension

Supuran

2015

Expert Review of Neurotherapeutics

139

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Idiopathic intracranial hypertension (IIH) is characterized by an increase of intracranial pressure in the absence of neurologic tumors. The sulfonamide carbonic anhydrase (CA, EC 4.2.1.1) inhibitor (CAI) acetazolamide (AAZ), a compound developed in the 1950s as a diuretic drug and presently used as an antiglaucoma, antiepileptic and diuretic agent, is effective in the treatment of IIH. AAZ is a low nanomolar inhibitor of CA isoforms involved in cerebrospinal fluid (CSF) secretion. Inhibition of brain/choroid plexus CA II, IV, VA and XII leads to a decreased CSF fluid secretion and control of the intracranial pressure. Although many sulfonamide/sulfamate CAIs are in clinical use for decades, apparently only AAZ is being currently used clinically for IIH. We speculate that more lipophilic CAIs such as methazolamide, zonisamide or topiramate should lead to a more effective control of increased intracranial pressure, thus having the opportunity to become useful in the management of IIH.

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“…Acetazolamide [ACZ] and quinine were identified as two candidate compounds, which largely fit the above criteria. This report describes the PK and urinary elimination characteristics for ACZ, Acetazolamide is a carbonic anhydrase (CA) inhibitor that has been used for >50 years to treat glaucoma, edema, epilepsy and altitude sickness at daily doses ranging from 250–750 mg 10,11 . Most of the reported drug interactions with ACZ result from alteration of bicarbonate concentration (bicarbonaturia and hypokalemia) 10 and are “on-target” effects that would not be expected to occur at sub-therapeutic doses.…”

Section: Introductionmentioning

confidence: 99%

A Pharmacokinetic Study Examining Acetazolamide as a Novel Adherence Marker for Clinical Trials

Hampson

Babalonis

Lofwall³

et al. 2016

J Clin Psychopharmacol

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Rationale Accurate assessment of medication adherence is critical for determination of medication efficacy in clinical trials, but most current methods have significant limitations. This study tests a sub-therapeutic (microdose) of acetazolamide as a medication ingestion marker, because acetazolamide is rapidly absorbed and excreted without metabolism in urine and can be non-invasively sampled. Methods In a double-blind, placebo-controlled, residential study, ten volunteers received 15 mg oral acetazolamide for four consecutive days. Acetazolamide pharmacokinetics were assessed on Day 3, and its pharmacokinetic and pharmacodynamic interactions with a model medication (30 mg oxycodone) were examined on Day 4. The rate of acetazolamide elimination into urine was followed for several days after dosing cessation. Results Erythrocyte sequestration (half-life= 50.2±18.5h, mean±SD, n=6), resulted in the acetazolamide microdose exhibiting a substantially longer plasma half-life (24.5±5.6 h, n=10) than previously reported for therapeutic doses (3–6 h). Following cessation of dosing, the rate of urinary elimination decreased significantly (F(3,23)=247: p<0.05, n=6) in a predictable manner with low inter-subject variability and a half-life of 16.1±3.8h (n=10). For each of four consecutive mornings after dosing cessation, the rates of urinary acetazolamide elimination remained quantifiable. There was no overall effect of acetazolamide on the pharmacodynamics, Cmax, Tmax or elimination half-life of the model medication tested. Acetazolamide may have modestly increased overall oxycodone exposure (20%, p<0.05) compared with one of the two days when oxycodone was given alone, but there were no observed effects of acetazolamide on oxycodone pharmacodynamic responses. Conclusions Co-formulation of a once-daily trial medication with an acetazolamide microdose may allow estimation of the last time of medication consumption for up to 96h post-dose. Inclusion of acetazolamide may, therefore, provide an inexpensive new method to improve estimates of medication adherence in clinical trials.

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Safety of carbonic anhydrase inhibitors

Cited by 57 publications

References 113 publications

Circumstances When Arterial Blood Gas Analysis Can Lead Us Astray

Circumstances When Arterial Blood Gas Analysis Can Lead Us Astray

Acetazolamide for the treatment of idiopathic intracranial hypertension

A Pharmacokinetic Study Examining Acetazolamide as a Novel Adherence Marker for Clinical Trials

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