Pharmacokinetic behaviour of ACP gel, an autocrosslinked hyaluronan derivative, after intraperitoneal administration.

ABSTRACT

Autocrosslinked polysaccharide (ACP) gel is a fully biocompatible cross-linked derivative of hyaluronic acid, which has prolonged in vivo residence time and improved mechanical properties with respect to native hyaluronan for use in various surgical applications. The objective of this study was to assess the pharmacokinetic behaviour of ACP gel in dogs after intraperitoneal administration. Seven beagle dogs received intraperitoneal injections of tritium-labelled ACP gel. Blood samples were taken, and urine and faeces were collected until sacrifice, scheduled at various time points from 3 to 192 h after administration. Organs were removed from the animals at autopsy. Bodily fluid and organ samples were analysed for total and non-volatile radioactivity. Non-volatile radioactivity slowly appeared in plasma, with a median T(max) of 12 h, and then declined with a mean half-life of 69 h. Total radioactivity in plasma peaked later and declined more slowly, consistent with the formation of tritiated water. Little non-volatile radioactivity was found in any organs except the liver, where about 16% of the dose was present 72 h after administration, and the intestines, where the presence of radioactivity was probably due to a retention effect. A minor amount of non-volatile radioactivity was also found in the bone marrow. In summary, ACP gel administered into the peritoneal cavity is removed slowly by active initial catabolism at the injection site, and is then catabolised by well described physiological pathway of hyaluronan degradation with final release of simple molecules such as CO(2) and H(2)O. Given its in vivo residence time, ACP gel may be considered an ideal implantable surgical device.