Pharmacokinetics of small unilamellar liposomes and incorporated lonazolac after i.m. administration

Abstract

The nonsteroidal anti-inflammatory drug lonazolac [3-(p-chlorphenyl)-l-phenylpyrazole-4]-acetic acid was incorporated into the bilayer of liposomes. The unilamellar and homogeneously sized liposomes with a diameter of 45 ± 7 nm were prepared by controlled detergent dialysis. The maximal amount of lonazolac incorporation is 0.140 mg per mg egg phosphatidylcholine (egg PC). The liposomes were stable over a year. Pharmacokinetics of the ³H-and ¹⁴C-labelled liposomes and of the ¹⁴C-labelled lonazolac was investigated after i.v. and i.m. administration to rabbits. The i.m. injected liposomes showed a terminal half-life of 74 h and after 24 h 7 per cent of the administered lecithin was still in the plasma. Eight hours following the i.m. injection of the liposomes, the plasma levels of lonazolac were significantly higher compared to the reference. A portion of the liposomes was released from the muscle into the circulation. A great share of lonazolac was quickly interchanged between the liposomes and the surrounding tissue. In additional experiments small oligolamellar liposomes should be used to decrease the interchange of lonazolac and to enhance the plasma levels of liposomal incorporated lonazolac.