614 BIOTIN 



cellular fragmentation at the periphery of sebaceoii.s glands, and the lipids 

 are apparently phagocytized by histiocytes. Lipids may also be found in 

 melanin-bearing cells around the sebaceous cells. ^ 



No specific changes were found in the nervous system or in the muscles 

 in biotin-deficient rats. The muscles may be atrophic but without signs of 

 true degeneration.^ 



XII. Pharmacology 



PAUL c;v()H(;v 



Administration of biotin either in a single massive dose or in multiple 

 large doses produces essentially no striking pharmacodynamic action.'' - 



Large single doses of rfZ-biotin (1 g. per kilogram) were without any 

 detectable toxic effect in mice. Multiple large doses gi\'en intravenously to 

 dogs or per os to mice and normal rats produced no signs of toxicity. 



Large doses of biotin had no effect on the blood pressure, heart rate, or 

 respiration in anesthetized cats or in rats. Relatively high concentrations 

 of biotin produced no effect on strips of guinea pig, rat, or rabbit uterus, 

 on rabbit or rat intestine, or on frog's heart when perfused in situ. 



No signs of local irritation were observed after application of biotin to 

 the cornea (rabbit) or after intradermal (guinea pigs) or intramuscular 

 (rabbit) injections. 



The secretion of free hydrochloric acid by the gastric glands appeared 

 to be depressed by f/-biotin. Renal function or metabolic rate remained 

 unchanged after administration of a large single oral dose of d-biotin. Re- 

 peated oral doses of biotin produced no changes in hepatic or renal function, 

 blood fibrinogen, rectal temperature, sensitivity of nerve endings, skin 

 regeneration, or healing of scalded skin in the normal rat. 



Pharmacological studies on biotin-deficient rats revealed a few interesting 

 facts.^ The amplitude of contractions of the isolated uterus or intestine of 

 the biotin-deficient rat is less than that of the noi'mal animal of the 

 same age. Biotin added to the Ringer-Locke solution in which the isolated 

 organs were suspended did not alter the contractions. 



The intravenous administration of large doses of biotin to the ane\sthe- 

 tized biotin-deficient animal has no effect on heart rat(>, blood prcssui'c, 



5 W. MontagiKi, Proc. Soc. Esptl. liinl. Med. 73, 127 (li)5()). 



« J. H. Shaw !uid P. H. Phillips, Pr„r. Soc. Exptl. Biol. Med. 51, 406 (1«)42). 



' J. L. Schmidt and IVI. i.ai.dy, I'nw. Soc. Exptl. Biol. Med. 49, 82 (1942). 



2 P. J. Crittenden, Arch. Intern. Fhar inacod ynamie 76, 417 (1948). 



3 P. J. Crittenden, Arch. Intern. Pharmacodynamie 77, 29 (1948). 



