THE ROLE OF THE LYMPHATIC-SYSTEM IN THE PRESYSTEMIC ABSORPTION OF FLUPHENAZINE AFTER INTRAMUSCULAR ADMINISTRATION OF FLUPHENAZINE DECANOATEIN RATS

Sprague Dawley rats (n = 16) were injected intramuscularly with fluphe nazine decanoate (78 mg/kg) in sesame oil. Groups of four rats were su rgically prepared on days 1, 7, 15 and 32 post-injection and samples o f lymph obtained from the thoracic duct. Fluphenazine was found in sim ilar concentrations in lymph and plasma, although the decanoate was no t detected in either body fluid. These data suggest that the lymphatic system plays a role in the presystemic absorption of fluphenazine aft er i.m. administration of fluphenazine decanoate in the rat. In vitro experiments showed that fluphenazine decanoate was very rapidly hydrol yzed when incubated with rat plasma (t(1/2) 0.6 h) or muscle homogenat es (t(1/2) 1.0 h). Rates of hydrolysis of fluphenazine decanoate were lower in dog muscle homogenates (t(1/2) 4.3 h), and very much lower wh en incubated with plasma from dog (t(1/2) 42.9 h) or humans (t(1/2) 50 .9 h).