RT Journal Article SR Electronic T1 In vivo safety of hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase in a large animal model for phenylketonuria. JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 598 OP 602 VO 224 IS 3 A1 C M Ambrus A1 S D Sharma A1 C Horváth A1 K Kalghatgi A1 S Anthone A1 J L Ambrus A1 C Cooley A1 E A Mirand YR 1983 UL http://jpet.aspetjournals.org/content/224/3/598.abstract AB Hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase (PAL) were developed for the in vivo depletion of phenylalanine (Phe) in circulating blood. A series of experiments was conducted with a large animal model in order to explore its safety for clinical use. The level of red blood cells, white blood cells and platelets did not change during a 2-hr application of the reactors in anesthetized, heparinized dogs and monkeys with experimental hyperphenylalaninemia. No increase in blood urea nitrogen was observed due to generation of ammonia from PAL-catalyzed Phe breakdown. The other metabolic product, trans-cinnamic acid, was reported to be nontoxic. Repeated application of the PAL-reactors to the same animals did not produce untoward physiological or immunological reactions. These data suggest that PAL-reactors may be safe for in vivo use to control excess Phe brought about by fever, infection or pregnancy in phenylketonuric individuals otherwise balanced by a Phe-poor diet. Application of PAL-reactors may serve as a model for extracorporeal enzyme replacement in enzyme-deficiency diseases.