Aniracetam is very rapidly and completely absorbed from the gastrointestinal tract. However, absolute systemic bioavailability is only about 0.2%. Aniracetam has a high volume of distribution (2.5 L/kg, which implies extensive extravascular distribution) and is very rapidly eliminated 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 (≈ 0.5 hours). Aniracetam is completely metabolised and the principal metabolites, N-anisoyl-γ-aminobutyric acid (N-anisoyl-GABA), 2-pyrrolidinone, succinimide and anisic acid, are excreted via the urine (84%), the faeces (2%) or as CO2 in expired air. After multiple dose administration, there is no indication of accumulation of drug or principal metabolites, with the exception of succinimide. Measurable concentrations of 2 main metabolites, N-anisoyl-GABA and 2-pyrrolidinone, were found in the cerebrospinal fluid of patients treated with aniracetam for 12 weeks.
KeywordsTotal Body Clearance Anisic Acid Succinimide Oral Dosage Form Aniracetam
Unable to display preview. Download preview PDF.
- Amakusa T, Iizuka R, Kuruma I, Uto M. Transfer to cerebrospinal fluid of aniracetam in cerebrovascular disease. Journal of Clinical Therapeutics and Medicines 3: 381–392, 1987Google Scholar
- Brandt R, Meyer J. Binding of Ro 13-5057 and of its pyrrolidinone metabolite to human plasma proteins. F. Hoffmann-La Roche (Basel) data on file. B-84’787; December 20, 1982Google Scholar
- Guenzi A, Zanetti M, Marini G, Lion P, Federspil G. Relative bioavailability of two new oral dosage forms (tablet /040 and sachet /043) of aniracetam (Ro 13-5057) relative to the 750mg sachet (/041). F. Hoffmann-La Roche (Basel) data on file. B-155’057: 1989aGoogle Scholar
- Guenzi A, Zanetti M, Marini G, Lion P, Federspil G. Relative bioavailability of two new oral dosage forms (sachet: /041 and /042) of aniracetam (Ro 13-5057) relative to the 500mg tablet (/006). F. Hoffmann-La Roche (Basel) data on file. B-155’058: 1989bGoogle Scholar
- Honma A, Ikeda K, Udo N, Sdamori M, Hasegawa K, et al. Aniracetam: clinical phase I study of aniracetam. Journal of Clinical Therapeutics and Medicines 2: 929–952, 1986Google Scholar
- Mayersohn M, Roncari G, Wendt G. Disposition pharmacokinetics and metabolism of aniracetam in animals. Drug Investigation (Suppl. 1): 73–95, 1993Google Scholar
- Roncari G, Hoevels B, Zumbrunnen R. Dose proportionality study of aniracetam following single oral doses of lg, 2g and 4g of Ro 13-5057 to six healthy volunteers. F. Hoffmann-La Roche data on file. B-104’488; August 19, 1984Google Scholar
- Wendt G, Albrecht C, Guldimann B, Ranalder U, Roncari G, et al. Pharmacokinetics of Ro 13-5057, aniracetam, after single 100mg intravenous and 1000mg oral doses to six healthy volunteers. F. Hoffmann-La Roche (Basel) data on file. B-104’600; Feb 10, 1983Google Scholar
- Wendt G, Ziegler WH, Trautmann KH, Flueckiger A. Disposition of 14C-aniracetam (Ro 13-5057/012) in two human volunteers (VP 4283A). F. Hoffmann-La Roche (Basel) data on file. B-104’617; August 20, 1986Google Scholar