This work aimed to investigate the pharmacokinetics of the N-phenylpiperazine antipsychotic prototype LASSBio-579 and to compare the results with those described for its bioisosteric derivative LASSBio-581. LASSBio-579 was administered to male Wistar rats as a 10 mg kg(-1) intravenous bolus and 30 and 60 mg kg(-1) intraperitoneal and 60 mg kg(-1) oral doses, and plasma concentrations were determined by a validated LC-MS/MS method. Individual plasma concentration-time profiles were evaluated by non-compartmental and compartmental analysis, using WinNonlin. LASSBio-579 plasma protein binding was 93 +/- 4%. After intravenous administration of 10 mg kg(-1), the Vd(ss) (0.6 +/- 0.2 L kg -1) and the t(1/2) (5.2 +/- 1.1 h) determined were smaller than those obtained after extravascular routes, but the CL(tot) (0.23 +/- 0.05 Lh(-1)kg(-1)) was statistically similar (alpha = 0.05). The intraperitoneal and oral bioavailability was around 1.7% and 0.6%, respectively. The plasma profiles obtained after intravenous and intraperitoneal administration of the compound were best fitted to a three-compartment and two-compartment lag-time open model, respectively. Brain tissue showed low penetration (6.3%) and t(1/2) of 1.1 h. Both the limited bioavailability and the lower brain penetration of LASSBio-579, in comparison with the LASSBio-581, suggest that its CNS activity may be due to a high receptor binding affinity or to a specific distribution into brain structures.