Neuromuscular recovery after peripheral nerve repair: effects of an orally-administered peptide in a primate model.
Oral delivery of the tripeptide calpain inhibitor, leupeptin, after median nerve transection and epineural nerve repair in primates (Cebus apella) was studied for its potential benefits to neuromuscular recovery. Results of a controlled, dose-response study indicated that leupeptin was absorbed into plasma by the oral route of administration. When plasma leupeptin concentrations were 3 micrograms/ml or greater, morphologic and functional motor recovery were facilitated after nerve repair. Serial testing in hematology, clotting, and serum biochemistry showed that there were no adverse effects, when leupeptin was administered twice daily for 6 months following nerve repair. These data indicate that leupeptin is an effective and safe pharmaceutic adjunct to nerve repair and may have clinical benefits in humans, where the oral route is a much preferred method of delivery.
Badalamente
M A
MA
Department of Orthopaedics, SUNY, Stony Brook 11794-8181, USA.
Hurst
L C
LC
Stracher
A
A
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002154:Calpain / Q000037:antagonists & inhibitors; D002428:Cebus; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007976:Leupeptins / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008475:Median Nerve / Q000187:drug effects* / Q000502:physiology / Q000601:surgery* / Q000648:ultrastructure; D008866:Microsurgery; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000294:innervation* / Q000502:physiology / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000187:drug effects; D009431:Neural Conduction; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D014945:Wound Healing
D007976:Leupeptins; D011480:Protease Inhibitors; D002154:Calpain; C032854:leupeptin