tetracycline and 1-4-dioxane

Adsorption of tetracycline from separate solutions of ethanol, p-dioxane, and chloroform onto synthetic hydroxyapatite (containing about 1.5 monolayer of physisorbed water) was studied in order to understand its interaction with bone and teeth. The adsorption isotherms of tetracycline are reversible and Langmuirian from ethanol and p-dioxane and are almost identical. The isotherm is irreversible from chloroform, and a constant amount of adsorbate is removed from the solutions above a certain concentration. The irreversibly adsorbed compound is completely desorbed by prolonged repeated washing with ethanol. An analysis of the reversible isotherms showed that at maximum coverage the ring or polycyclic structure of the molecule stands perpendicular to the surface with appropriate hydroxyl groups and keto-oxygens hydrogen bonded to the surface. However, the adsorption from chloroform is irreversible and at maximum adsorption is about one and half times larger than that from either ethanol or p-dioxane. The process of adsorption does not affect the chemical integrity of tetracycline.

Topics: Adsorption; Bone and Bones; Chloroform; Dioxanes; Durapatite; Ethanol; Hydroxyapatites; In Vitro Techniques; Solutions; Tetracycline; Tooth

Aluminum (Al) solubilization from Al borate and its distribution in an octanol/aqueous system (Do/w) were determined in the absence and presence of 12 potential Al chelators. Citrate, N,N'-bis-(2-hydroxybenzyl)ethylenediamine- N,N'-diacetic acid (HBED), cyclohexane-1,2-diaminotetraacetic acid (CDTA), diethylenetriaminepentaacetic acid (DTPA), nitrilotriacetic acid (NTA), desferrioxamine, and ethylenediamine-N,N'-bis(2-dihydroxyphenylacetic acid) (EDDHA) were 55 to over 100% efficient in solubilizing equimolar amounts of Al. Tetracycline, EDTA, and 2,3-dihydroxybenzoic acid (DHBA) were less than 20% efficient. 1,4-Dioxane and fluoride were ineffective. The Do/w of Al averaged 0.005. The Do/w of the Al.chelator complex was generally less than that of Al, except for HBED and tetracycline (0.04 and 0.96, respectively). The Do/w of DHBA, desferrioxamine, EDDHA, and HBED were not influenced by Al, but tetracycline became more lipophilic. These compounds were tested for their ability to increase urinary Al excretion in Al-loaded rabbits. Chelators were given po weekly beginning 2 weeks after Al loading. Urine was obtained hourly from 3 hr prior to 6 hr after chelator administration and analyzed for Al. Fluoride and tetracycline (450 and 4500 mumol/kg) and citrate, NTA, EDTA, CDTA, DTPA, DHBA, HBED, and 1,4-dioxane (150 and 1500 mumol/kg) were ineffective. Following HBED administration, some of the Al-loaded rabbits died, presumably due to redistribution of Al within the rabbit. Following DTPA administration, some of the Al-loaded rabbits died, presumably due to DTPA. Oral EDDHA (1500 mumol/kg) significantly increased urinary Al excretion. EDDHA and desferrioxamine (150 mumol/kg) were administered by po, sc, and iv routes and were found to have comparable potency. The in vitro results may explain some of the in vivo findings. The in vitro methods may be useful to screen out compounds with no chelation potential. EDDHA-like compounds may have potential as alternatives to desferrioxamine in the prevention or treatment of Al accumulation and Al-induced toxicity.

Topics: Aluminum; Animals; Carboxylic Acids; Chelating Agents; Deferoxamine; Dioxanes; Models, Biological; Octanols; Rabbits; Structure-Activity Relationship; Tetracycline; Thermodynamics; Water