The pharmacology of intraperitoneally administered bleomycin

The clinical pharmacology of intraperitoneally administered bleomycin was examined in 11 patients with malignancies confined predominantly to the peritoneal cavity. Bleomycin (60 mg/m2) was mixed in 2 L of 0.9% NaCl, and administered rapidly into the peritoneal cavity via a Port-a-Cath (Pharmacia Nu Tech, Inc, Walpole, MA). The cavity was drained following either a four- or eight-hour dwell time. Bleomycin concentration in the peritoneal cavity and plasma was determined by radioimmunoassay. A total of 15 courses was studied. The peak peritoneal: plasma concentration ratio averaged 22, and total exposure for the peritoneal cavity averaged seven-fold greater than that for the plasma. The peritoneal and plasma half-lives for bleomycin were 3.2 and 6.0 hours, respectively. The peritoneal clearance of bleomycin averaged 11.3 mL/min/m2. Abdominal pain occurred on 47% of courses; other toxicities included fever, skin rash, and mucositis. We conclude that there is a substantial pharmacologic advantage to the peritoneal route for tumors confined to the peritoneum, but that the advantage is less, and the local toxicity greater, than that found with the intraperitoneal administration of many other anticancer drugs.