Intraperitoneal drug administration

Intraperitoneal drug administration is not common. It is used pedominantly to administer compounds during preclinical discovery and development. Its clinical use is generally limited to chemotherapy for tumors with peritoneal involvement. 

Intraperitoneal (IP) A route of drug administration for a drug to an animal by direct injection into the peritoneal cavity. 

SAFETY PROFILE Confirmed carcinogen. US Food and Drug Administration recommends removal from laxative formulations. Moderately toxic by intraperitoneal route. Human systemic effects changes in urine composition, gastritis, nausea or vomiting. Used in medicine as a laxative in chemistry as an indicator. When heated to decomposition it emits acrid smoke and irritating fumes. 

After anesthesia was induced with ethyl ether in ten 200-g Wister male rats (CLEA Japan Inc., Tokyo, Japan), their backs were shaved and an incision (2-cm long and 2-cm deep) was made. The polymer films (1.0 X 0.5 cm), which were sterilized with ethylene oxide gas, were subcutaneously implanted. An antibacterial drug, piperacillin sodium 20 mg/kg (Sankyo Pharmaceutical Co., Tokyo, Japan), was administered intraperitoneally once after the implantation procedure. Neither cleaning of the implanted site nor further drug administration was made throughout the implantation period. 

A pro-drug approach for improving the pharmacokinetics of zanamivir has recently shown some promise. The alkoxyalkyl ester 23 of zanamivir, with long alkyl chains chosen to counteract the high hydrophUicity of the molecule, was reported to show significant protective effects against influenza (HlNl) infection in mice upon oral or intraperitoneal administration (Liu et al. 2007). 

In this section the intraperitoneal route of liposome administration will be discussed. For a number of diseases this route of administration may be preferred over the intravenous route of administration of liposomes. For example, intraperitoneal injection of drug-... 

Intraperitoneal administration of chemotherapeutic agents has been used for many years as a way of increasing the delivery of drugs to tumors (e.g., ovarian carcinoma) located in the peritoneal cavity (Markman, 1986 Howell and Zimra, 1988). Cisplatin (Casper et al., 1983 Markman et al., 1985), cytosine arabinoside (Ara-C) (King et al., 1984 Markman et al., 1985, 1986), and bleomycin (Markman et al., 1986) are examples of intraperitoneally administered drugs which were already successfully applied in clinical settings. 

In comparison with the intravenous route of administration the potential advantages of intraperitoneal therapy are the avoidance of high toxic drug plasma levels and an increased (local) exposure of tumors (cells) to anticancer drugs. Whether this increased exposure... 

Several studies have been performed in order to investigate the effect of liposomal size (Hirano and Hunt, 1985), lipid composition (Senior and Gregoriadis, 1982 Hirano et al., 1985), and lipid dose (Ellens et al., 1983, Kim et al., 1987) on the fate of liposomes after intraperitoneal administration. In the size range studied (0.048-0.72 Min), no size-dependent absorption could be expected (Hirano and Hunt, 1985). Particles larger than 22.5 pm are not expected to enter the lymphatic capillaries (Allen, 1956). After intraperitoneal administration of multivesicular liposomes (19 + 7 ym), Kim and Howell (1987a) and Kim et al. (1987) showed that liposomal entrapment of Ara-C prolongs the half-Ufe of the drug in the peritoneal... 

Kim et al. (1987) showed that the prolonged retention time of Ara-C in the peritoneal cavity after intraperitoneal administration of the drug in liposomal form as discussed above resulted in better therapeutic effects on intraperitoneally inoculated L1210 cells, as compared to the free drug. The activity of intraperitoneally administered cDDP on Ehrlich ascites carcinoma in mice was increased after encapsulation in neutral liposomes (Sur et al., 1983). The in vivo studies revealed improved antitumor activity and a lower toxicity sifter administration of cDDP liposomes compared to free drug. 

Parker, R. J., Priester, E. R., and Sieber, S. M. (1982). Comparison of lymphatic uptake metabolism, excretion, and biodistribution of free and liposome-entrapped (l cjcytosine beta-D-arabinofuranoside following intraperitoneal administration in rats, Drug. Me tab. Dispos., 10, 40-46. 

Convenient intraperitoneal route of administration of drugs such as antibiotics and insulin. 

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