HUMAN PHARMACOKINETICS OF ANIRACETAM

Aniracetam is very rapidly and completely absorbed from the gastrointe stinal tract. However, absolute systemic bioavailability is only about 0.2%. Aniracetam has a high volume of distribution (2.5 L/kg, which i mplies extensive extravascular distribution) and is very rapidly elimi nated from the body. Indeed, total body clearance from blood (10 L/min ) exceeds cardiac output (implying that the lung is a major clearance organ) and plasma elimination half-life is very short (almost-equal-to 0.5 hours). Aniracetam is completely metabolised and the principal me tabolites, N-anisoyl-gamma-aminobutyric acid (N-anisoyl-GABA), 2-pyrro lidinone, succinimide and anisic acid are excreted via the urine (84%) , the faeces (2%) or as CO2 in expired air. After multiple dose admini stration, there is no indication of accumulation of drug or principal metabolites, with the exception of succinimide. Measurable concentrati ons of 2 main metabolites, N-anisoyl-GABA and 2-pyrrolidinone, were fo und in the cerebrospinal fluid of patients treated with aniracetam for 12 weeks.