PT  - JOURNAL ARTICLE
AU  - C M Ambrus
AU  - S D Sharma
AU  - C Horváth
AU  - K Kalghatgi
AU  - S Anthone
AU  - J L Ambrus
AU  - C Cooley
AU  - E A Mirand
TI  - In vivo safety of hollow fiber enzyme-reactors with immobilized phenylalanine ammonia-lyase in a large animal model for phenylketonuria.
DP  - 1983 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 598--602
VI  - 224
IP  - 3
4099  - http://jpet.aspetjournals.org/content/224/3/598.short
4100  - http://jpet.aspetjournals.org/content/224/3/598.full
SO  - J Pharmacol Exp Ther1983 Mar 01; 224
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.