Tetracycline is absorbed from the dog stomach, duodenum and ileum hut relatively little absorption occurs from the colon. Absorption from the small intestine is extremely rapid, peak serum levels being attained within 30 minutes. Absorption from the stomach is remarkable but peak levels are reached much more slowly than from the intestine and are maintained for a considerably longer time. The actual amount of tetracycline which is absorbed during the period examined is small in relation to the dose administered. Absorption appears to be a passive diffusion phenomenon. Excretion data on tetracycline are presented. Fifty to 60% of an intravenously administered dose is consistently excreted within 24 hours regardless of the initial dose. Another 20 to 25% is excreted in the next 48 to 72 hours. Renal clearance data provide a total tetracycline/creatinine ratio of 0.33 in unanesthetized dogs. Protein binding studies indicate that 69% of the blood complement of tetracycline is protein bound. Assuming that in vitro protein binding data reliably reflect the amount of drug filterable at the glomeruli, the filterable tatracycline/creatinine ratio then becomes 1.04. Considering all of the evidence presented, it is concluded that the renal excretion of tetracycline occurs solely by way of glomerular filtration with the tubules playing littleor no role.

Annals of the New York Academy of SciencesVolume 76, Issue 2 p. 44-65 PHARMACOLOGICAL STUDIES WITH KANAMYCIN D. E. Tisch, D. E. Tisch Research Division, Bristol Laboratories Inc., Syracuse, N. Y.Search for more papers by this authorJ. B. Huftalen, J. B. Huftalen Research Division, Bristol Laboratories Inc., Syracuse, N. Y.Search for more papers by this authorH. L. Dickison, H. L. Dickison Research Division, Bristol Laboratories Inc., Syracuse, N. Y.Search for more papers by this author D. E. Tisch, D. E. Tisch Research Division, Bristol Laboratories Inc., Syracuse, N. Y.Search for more papers by this authorJ. B. Huftalen, J. B. Huftalen Research Division, Bristol Laboratories Inc., Syracuse, N. Y.Search for more papers by this authorH. L. Dickison, H. L. Dickison Research Division, Bristol Laboratories Inc., Syracuse, N. Y.Search for more papers by this author First published: September 1958 https://doi.org/10.1111/j.1749-6632.1958.tb54692.xCitations: 30AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume76, Issue2The Basic and Clinical Research of the New Antibiotic, KanamycinSeptember 1958Pages 44-65 RelatedInformation

Ambucetamide, 2-(di-n-butylamino)-2-(4-methoxyphenyl)-acetamide, has been found to have antispasmodic action on the uterus. Direct comparison of ambucetamide and papaverine on the same isolated, rat-uterine preparation indicated that they possessed activity of the same magnitude. On intact rat-uterine preparations, ambucetamide caused a decrease in the amplitude and frequency of contractions with an elevation in tone in about half the animals while the other half showed no effect. In the majority of the dogs studied, ambucetamide reduced the tone of the uterus and increased the amplitude of contractions. Uterine tone was also decreased following oral administration. The tone of the dog ileum was decreased following an intravenous dose of 5.0 mg./Kg. and type III contractions frequently appeared. A moderate decrease in blood pressure persisting for about one-half hour was also observed at this dose. Chronic toxicity studies were carried out in both rats and dogs. None of these animals developed any functional abnormalities nor did they show any gross or microscopic pathology at autopsy.

1. DL-alpha, alpha-diphenyl, gamma-dimethylaminovaleramide, Centrine (previously referred to as BL-139), shows approximately one-half the activity of atropine and one-fifth the activity of papaverine on isolated guinea pig and rabbit ileum strips. 2. Centrine causes a decrease in tone and a reduction in activity of most portions of the gastro-intestinal tract. It effectively counteracts the spasmogenic responses to acetylcholine and arecoline. 3. Oral administration requires very little increase in dosage to obtain responses comparable to those following intramuscular or intravenous administration. 4. Centrine is more effective in decreasing the activity of the intact colon than either atropine or Banthine and also has a greater duration of action. 5. Centrine is slightly less active than atropine in blocking the vasodepressor responses to acetylcholine and arecoline. Atropine is at least four times more active in blocking the effects of vagal stimulation on the heart. 6. Centrine has less mydriatic and salivary effects than atropine. 7. Dogs tolerate prolonged daily oral feedings of 25 mgm./kgm. of Centrine. Higher doses produce drying of the mucous surfaces. Prolonged daily oral administration of doses up to 50 mgm./kgm. does not produce any gross or microscopic abnormalities.

5-(1-Cyclohexen-1-yl)-5-methyl barbituric acid ("nor-evipal") is excreted unchanged in the urine of dogs in 13 per cent yield. An additional 20 per cent is excreted in the form of a new substance ("keto-nor-evipal") in which the cyclohexenyl ring has been oxidized presumably to a cyclohexenonyl group. After administration of 5-(1-cyclohexen-1-yl)-1,5-dimethyl barbituric acid (hexobarbital, Evipal) to dogs, only traces of unchanged material and of norevipal were present in the urine. Keto-nor-evipal was isolated in 5 to 6 per cent yield. Two additional products ("keto-evipal I" and "keto-evipal II") were isolated in small amounts. These appear to be isomeric cyclohexenonyl derivatives of Evipal. These oxidized products are inactive as anesthetics. Comparison of the amounts of the several products from Evipal with the amounts of those products from nor-Evipal shows that primary demethylation of Evipal occurs to an extent of only about 2 per cent and that primary oxidation of Evipal occurs to an extent of at least 8 per cent. The fates of about 90 per cent of the Evipal and of about 70 per cent of the norevipal are still unknown.

We have found a number of solvents which seem to be suitable for the administration of the water-insoluble acid-form of certain barbituric acid derivatives. The most versatile of these solvents are paraldehyde and triacetin. Because we do not know the pharmacology of triacetin, we have concentrated our present studies on solutions in paraldehyde. A 30% solution in paraldehyde of 5 -allyl- 5 -( 1 -methylbutyl)-barbituric acid seems suitable for the production of any desired degree of hypnosis or anesthesia by intramuscular or intravenous injection. This solution has these advantages over the commonly used aqueous alkaline solutions of barbituric acids: it can be sterilized by heat and remains stable for a long time; it is so slightly irritating that anesthetic doses can be injected intramuscularly without discomfort; the anesthetic dose is contained in a relatively small volume. For intravenous injection it is possible that corresponding solutions of 1 -methyl- 5 -allyl- 5 -isopropyl-barbituric acid (narconumal) and of 1 -methyl- 5 -ethyl- 5 -( 1 -methylbutyl)-barbituric acid would also be suitable for the production of relatively short anesthesia, to be lengthened if desired by supplemental injections.

The optically isomeric sec. -butyl alcohols are very nearly equal in anesthetic activity as measured in mice.