PHARMACOKINETICS OF TRANSPERITONEAL INSULIN TRANSPORT

Seven type I insulin-dependent diabetic patients on continuous ambulat ory peritoneal dialysis treatment were selected for this study. Each p atient participated in three different 6-hour 'single-dwell' studies o n 3 consecutive days. A mean dose of 33 +/- 1.3 U Insulin Actrapid Hum an was given intraperitoneally each day. The procedures for intraperit oneal insulin administration were: (1) with 1,000 ml Ringer lactate; ( 2) with 1,000 ml 3.86% glucose-containing dialysate, and (3) into an e mpty peritoneal cavity. The calculation of the intraperitoneal volume was done with a single injection indicator dilution technique in which 100 kB(q) radioiodinated serum albumin (RISA) was added into the flui d prior to instillation. Free insulin and glucose were analyzed at 16 time intervals in blood and in dialysate during each dwell. After drai nage the peritoneal cavity was rinsed with 1,000 ml Ringer lactate fol lowed by two consecutive 5-hour exchanges with 2,000 ml glucose-contai ning dialysate. Recovery of insulin and RISA was measured in rinsing f luid and in sampled dialysate during the 6-hour dwell. The kinetic cal culations made for insulin were disappearance rate (mU/min) from the p eritoneal cavity, and appearance rate in circulating blood. After drai nage and rinsing, 66.0 +/- 10 and 71.8 +/- 9.8% of the insulin instill ed had disappeared after 6 h from the glucose fluid and from the Ringe r solution respectively and did not differ significantly. However, the estimated disappearance rate from the peritoneal cavity was significa ntly higher in Ringer than in glucose from the time interval 120 to 36 0 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-m l fluid volume. However, a higher blood concentration was also found w hen Ringer was instilled than when a hyperosmolal glucose solution was instilled. A high first-pass elimination in the liver is suggested. I n conclusion, fluid volume and also the osmolality of the solution in the peritoneal cavity decreases the transport rate, but not the bioava ilability of insulin given intraperitoneally. Both a high peak shape a nd a continuous insulin appearance in blood can be achieved. It is sug gested that there is a high first-pass elimination of insulin during a bsorption from the peritoneal cavity. However, the values are uncertai n and extended investigations must be done.