Figure 22

Pharmacokinetics of the peritoneal plasma barrier after systemic mitomycin C administration. The plasma area under the curve is very similar to the peritoneal fluid area under the curve. This represents the mean of 15 cycles of intravenous mitomycin C in seven patients. Interestingly, at three hours the IV and IP concentrations cross. After three hours, there is a sequestering of chemotherapy within the peritoneal space. It should be noted that these studies were performed after an intravenous infusion of mitomycin C that was performed over two hours. From Sugarbaker PH, Stuart OA, Vidal-Jove J, Pessagno AM, and DeBruijn EA: Pharmacokinetics of the peritoneal plasma barrier after systemic mitomycin C administration (In) Sugarbaker PH (Ed): Peritoneal Carcinomatosis: Drugs and Diseases. Kluwer: Boston p 45, l996.

Figure 23

Pharmacokinetics of the peritoneal plasma barrier after systemic mitomycin C administration in a patient with extensive peritoneal stripping. In patients who have extensive intraabdominal adhesions, the delivery of mitomycin C chemotherapy intravenously is superior to the delivery of drug to peritoneal surfaces. This patient had a two-hour infusion of mitomycin C, and mitomycin C concentrations were measured over six hours in both plasma and in peritoneal fluid. The AUC plasma to peritoneal fluid is 2:1. From Sugarbaker PH, Stuart OA, Vidal-Jove J, Pessagno AM, DeBruijn EA: Pharmacokinetics of the peritoneal plasma barrier after systemic mitomycin C administration (In) Sugarbaker PH (ed): Peritoneal Carcinomatosis: Drugs and Diseases. Kluwer: Boston p 48, 1996.

Figure 24

Pharmacokinetics of intraperitoneal 5-fluorouracil. 5-FU was placed in 1.5 liters of fluid and instilled rapidly into the abdominal cavity. Drug concentrations in peritoneal fluid, portal plasma and systemic plasma were determined. Area under the curve of peritoneal fluid to systemic plasma is approximately 250. Area under the curve of portal plasma to systemic plasma is approximately 10. Increased concentrations of 5-fluorouracil in both peritoneal fluid and portal blood result from the intraperitoneal instillation of 5-fluorouracil. From Sugarbaker PH, Graves T, DeBruijn EA, Cunliffe WJ, Mullins RE, Hull WE, Oliff L, Schlag P: Early postoperative intraperitoneal chemotherapy as an adjuvant therapy to surgery for peritoneal carcinomatosis from gastrointestinal cancer: Pharmacologic studies. Cancer Research 50:5790-5794, 1990.

Figure 25

Intraperitoneal 5-fluorouracil given on day 1 and day 5 postoperatively. There is an increased clearance from peritoneal cavity to plasma on day 5, presumably a result of inflammation of the healing peritoneal surfaces. Nevertheless, the marked pharmacologic advantage of intraperitoneal drug administration remains. From Sugarbaker PH, Klecker RW, Gianola FJ, Speyer JL: Prolonged treatment schedules with intraperitoneal 5-fluorouracil diminished the local-regional nature of drug distribution. American Journal of Clinical Oncology 9:1-7, 1986.

Figure 26

Pharmacokinetics of intraperitoneal 5-fluorouracil in the early postoperative period after surgery alone or after surgery plus heated intraoperative intraperitoneal mitomycin C chemotherapy. Control patients had cytoreductive surgery alone. Patients with heated intraoperative intraperitoneal chemotherapy (HIIC) had heated intraoperative intraperitoneal mitomycin C. In the postoperative period; both groups had the concentration of 5-fluorouracil determined in the peritoneal fluid (perfusate) and in the plasma. There was a statistically significant difference between the control and intraoperative chemotherapy patients. However, the marked pharmacologic benefits of intraperitoneal 5-fluorouracil remains after heated intraoperative intraperitoneal chemotherapy with mitomycin C. From Jacquet P, Averbach A, Stephens AD, Stuart OA, Chang D, Sugarbaker PH: Heated intraoperative intraperitoneal mitomycin C and early postoperative intraperitoneal 5-fluorouracil: Pharmacokinetics studies. Oncology 1997 (in press).

Figure 27

Pharmacokinetics of early postoperative intraperitoneal 5-fluorouracil compared to delayed intraperitoneal 5-fluorouracil. The top graph shows the pharmacokinetics of intraperitoneal 5-fluorouracil with the drug instilled on the second postoperative day. The lower graph shows the pharmacokinetics of intraperitoneal 5-fluorouracil when the drug is infused into the peritoneal cavity two months after a surgical procedure. The pharmacology of intraperitoneal 5-fluorouracil is extremely stable over time.