Human Pharmacokinetics of Aniracetam
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.
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- 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