Pharmacokinetics of transperitoneal insulin transport.
Seven type I insulin-dependent diabetic patients on continuous ambulatory peritoneal dialysis treatment were selected for this study. Each patient participated in three different 6-hour 'single-dwell' studies on 3 consecutive days. A mean dose of 33 +/- 1.3 U Insulin Actrapid Human was given intraperitoneally each day. The procedures for intraperitoneal insulin administration were: (1) with 1,000 ml Ringer lactate; (2) with 1,000 ml 3.86% glucose-containing dialysate, and (3) into an empty peritoneal cavity. The calculation of the intraperitoneal volume was done with a single injection indicator dilution technique in which 100 kBq radioiodinated serum albumin (RISA) was added into the fluid prior to instillation. Free insulin and glucose were analyzed at 16 time intervals in blood and in dialysate during each dwell. After drainage the peritoneal cavity was rinsed with 1,000 ml Ringer lactate followed by two consecutive 5-hour exchanges with 2,000 ml glucose-containing dialysate. Recovery of insulin and RISA was measured in rinsing fluid and in sampled dialysate during the 6-hour dwell. The kinetic calculations made for insulin were disappearance rate (mU/min) from the peritoneal cavity, and appearance rate in circulating blood. After drainage and rinsing, 66.0 +/- 10 and 71.8 +/- 9.8% of the insulin instilled had disappeared after 6 h from the glucose fluid and from the Ringer solution respectively and did not differ significantly. However, the estimated disappearance rate from the peritoneal cavity was significantly higher in Ringer than in glucose from the time interval 120 to 360 min. A high and peak-shaped insulin concentration in the plasma was found following insulin injection into an empty peritoneal cavity, and was significantly higher than when insulin was dissolved in a 1,000-ml fluid volume. However, a higher blood concentration was also found when Ringer was instilled than when a hyperosmolal glucose solution was instilled. A high first-pass elimination in the liver is suggested. In conclusion, fluid volume and also the osmolality of the solution in the peritoneal cavity decreases the transport rate, but not the bioavailability of insulin given intraperitoneally. Both a high peak shape and a continuous insulin appearance in blood can be achieved. It is suggested that there is a high first-pass elimination of insulin during absorption from the peritoneal cavity. However, the values are uncertain and extended investigations must be done.
Department of Nephrology and Endocrinology, University Hospital, Trondheim, Norway.
T E
TE
Widerøe
K J
KJ
Dahl
L C
LC
Smeby
T
T
Balstad
S
S
Cruischank-Flakne
I
I
Følling
O
O
Simondsen
J
J
Ahlmen
S
S
Jørstad
D000328:Adult; D000368:Aged; D001798:Blood Proteins / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000628:therapy*; D003928:Diabetic Nephropathies / Q000097:blood / Q000628:therapy*; D005260:Female; D006207:Half-Life; D006801:Humans; D007263:Infusions, Parenteral; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007330:Insulin Antibodies / Q000097:blood; D061389:Insulin, Regular, Pork; D007457:Iodine Radioisotopes; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010529:Peritoneal Cavity; D010531:Peritoneal Dialysis, Continuous Ambulatory; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use
D001798:Blood Proteins; D002096:C-Peptide; D007328:Insulin; D007330:Insulin Antibodies; D061389:Insulin, Regular, Pork; D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; C000006:insulin, neutral