Pharmacokinetics and tissue distribution of olanzapine in rats

Autor: Yaroslav Teper, Manickam Aravagiri, Stephen R. Marder
Rok vydání: 1999
Předmět:
Zdroj: Biopharmaceutics & Drug Disposition. 20:369-377
ISSN: 1099-081X
0142-2782
Popis: The single dose pharmacokinetics of olanzapine in rats, following an oral dose and its distribution in the brain and other tissues after repeated oral and intra-peritoneal (i.p.) administration, were studied. Olanzapine in plasma, brain, liver, lung, kidney, spleen and fat was assayed at predose, 0.25, 0.5, 1, 2, 5, 12, 24, 36, 48 h postoral dose of 6 mg/kg and after daily oral and i.p. doses of 0.25, 1, 3, and 6 mg/kg/day of olanzapine for 15 consecutive days by a sensitive and specific HPLC method with electrochemical detection. Olanzapine was readily absorbed and distributed in plasma and tissues as the peak concentrations were reached within approximately 45 min after the oral dose. The terminal half-life of olanzapine in plasma was 2.5 h and in tissues it ranged from 3 to 5.2 h. The area under the concentration-time curve (AUC(last)) was lowest in plasma and largest in liver and lung. The AUC(last) of olanzapine was eight times larger in brain and three to 32 times larger in other tissues than that in plasma. After repeated oral doses, the plasma and tissue concentrations of olanzapine were generally higher than those after repeated i.p. doses. The liver and spleen had the highest concentrations after oral and i.p doses, respectively. In both cases, the tissue concentrations were four- to 46-fold higher than that in plasma and correlated with administered doses. Likewise, plasma concentrations strongly correlated with the simultaneous brain and tissue concentrations (r(2)>0.908, p
Databáze: OpenAIRE
Externí odkaz: