Absorption studies with porcine pancreatic kallikrein in man
Miska, W.; Geiger, R.; Schill, W.B.
Agents and Actions. Supplements 38(Part 2): 136-143
1992
ISSN/ISBN: 0379-0363 PMID: 1462822 Document Number: 3348
Porcine pancreatic kallikrein (PPK), the main component of Padutin (Bayropharm, FRG), is used since 1974 for the treatment of some forms of idiopathic infertility in man. During kallikrein therapy the number of spermatozoa increases, and qualitative and quantitative sperm motility is improved. In order to investigate the intestinal absorption of PPK in man a clinical study with 7 healthy volunteers was performed. 4500 KE (corresp. to 2.8 mg PPK) and 600 KE (corresp. to 0.38 mg PPK) of kallikrein respectively was orally adminstered in one dosis. Serum and urine samples were collected several times within 24 hours. Seminal plasma was collected 4-5 days before and 8 hours after treatment with kallikrein. Absorbed PPK was determined using a highly sensitive bioluminescence-enhanced enzyme immunoassay and a newly developed light measuring equipment (MTP reader). The limit of detection was 1 pg/ml in serum corresponding to 6 amol PPK per assay. For both groups (600 KE and 4500 KE) absorption of PPK in serum was found. Maximum absorption was observed between 4 and 12 h and between 2 and 6h, respectively, after oral application of kallikrein. Renal excretion plays no important role in the elimination of PPK from serum. In gel filtration experiments with blood samples of volunteers in which absorbed PPK was detected, one peak of immunochemically active material corresponding to a molecular mass of 82 kDa was found. According to our results, kallikrein is absorbed in unaltered form by the intestine. The absorbed amount of PPK is sufficient to exert a possible effect in enzymatically active form on the target cells in the male gonads before it is inhibited probably by al-proteinase inhibitor. Porcine pancreatic kallikrein is absorbed intestinally in unaltered form and is slowly inhibited in serum probably by al-proteinase inhibitor. The absorbed amount of PPK is sufficient to exert a possible effect in enzymatically active form on the target cells in the male gonads for several hours. For the elimination of kallikrein from serum renal excretion plays only a minor role.
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