PubMed · 14272502
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P DAVID, N AERICHIDE. 1965-04-10. DIURETICS.. https://pubmed.ncbi.nlm.nih.gov/14272502/
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The aim of this study was to prepare and evaluate Eudragit (RS and RL) microspheres containing acetazolamide. Microspheres were prepared by solvent evaporation method using acetone/liquid paraffin system. The influence of formulation factors (stirring speed, polymer:drug ratio, type of polymer, ratio of the combination of polymers) on particle size, encapsulation efficiency and in vitro release characteristics of the microspheres were investigated. The yields of preparation and the encapsulation efficiencies were high for all formulations the microspheres were obtained. Mean particle size changed by changing the polymer:drug ratio or the stirring speed of the system. Although acetazolamide release rates from Eudragit RS microspheres were very slow and incomplete for all formulations, they were fast from Eudragit RL microspheres. When Eudragit RS was added to Eudragit RL microsphere formulations, release rates slowed down and achieved the release profile suitable for peroral administration.
The accurate determination of cerebrovascular reserve (CVR), especially in elderly subjects, entails several technical issues. From a review of the literature, the optimal technique employs quantitative 15O-water PET imaging determinations of cerebral blood flow (CBF) and acetazolamide (ACZ) (1 g iv with measurements at 10- to 20-min post-administration) as the vasodilating agent. CBF and CVR measurements were made using this methodology on 12 elderly subjects (3 males, 9 females, 66-84 years of age) meeting criteria for mild cognitive impairment (MCI) without other significant medical problems. Applying this quantitative technique, the cognitive and emotional status of the subject during the imaging procedure influenced the magnitude of the measurements. The semiquantitative measures resulted in even more pronounced subject state influences. The conditions under which CBF or CVR measurements are made should be controlled and reported. If semiquantitative techniques (e.g., single-photon emission-computed tomography [SPECT] imaging) must be employed for the determination of CVR, the validity of any measurement is dependent on the careful control of the general physiological status (e.g., heart rate, blood pressure, level of anxiety) of the patient.
In a randomized, double-blind cross-over study 10 subjects were exposed to a simulated altitude of 4500 m for 10 h after administration of placebo, acetozolamide (250 mg bid) or theophylline (250 mg bid). T2-weighted magnetic resonances images (MRI) and diffusion weighted MRI were obtained directly after exposure to altitude under hypoxic conditions. Although eight of 10 subjects had moderate to severe acute mountain sickness (AMS), we found no evidence of cerebral oedema, irrespective of the medication taken. Almost all subjects showed a decrease in inner cerebrospinal fluid (iCSF) volumes (placebo - 10.3%, P= 0.02; acetazolamide - 13.2%, P= 0.008, theophylline -12.2%, n.s.). There was no correlation between AMS symptoms and fluid shift. However, we found a significantly positive correlation of large (>10 ml) iCSF volume and more severe AMS after administration of placebo (r = 0.76, P= 0.01). Moderate to severe AMS after high altitude exposure for 10 h is associated with a decreased iCSF-volume independent of AMS severity or medication without signs of cerebral oedema.