THE EXCRETION AND DISTRIBUTION IN BODY FLUIDS OF TETRACYCLINES AFTER INTRAVENOUS ADMINISTRATION TO DOGS

¹ Medical Research Laboratories, Chas. Pfizer & Co., Inc., Groton, Connecticut

6-Methyleneoxytetracycline, MOTC (methacycline), was studied in dogs after intravenous administration and compared with 6-demethyl-chlortetracycine, DMCT (Declomycin), -6-deoxyoxytetracycline, DOOTO, oxytetracycline, OTO (Terramycin) and 6-demethyl-6-deoxytetracycline, DMDOTC.

The high serum concentrations obtained with MOTO, as well as the serum concentrations of the other tetracyclines, were explained by the combination of lipoid-solubilities with serum protein binding factors of the drugs. It is suggested that a highly lipoid-soluble tetracycline is concentrated in tissues to a greater extent than a less lipoid-soluble analog and therefore gives lower free drug concentrations in serum. Although two tetracydlines may show similar free drug concentrations because of similar lipoid-solubilities, the more highly serum protein bound gives higher serum concentrations.

Some tetracyclines interact with serum proteins of one species more extensively than with serum proteins of another species. The binding of MOTC by canine serum proteins is particularly high.

Less than 5% of administered dose of the tetracydlines tested was secreted into the bile within the first 24 hours.

The rate of disappearance of readily available DOOTO from the canine body by other than the renal route is higher than for MOTC, DMCT, and OTC. OTC shows the highest urinary excretion rate because it gives the highest free drug concentrations.