Source: European Medicines Agency (EU) Publisher: Desma GmbH, Peter-Sander-Str. 41b, 55252, Mainz-Kastel, Germany, Tel: +49 (0) 6134 21079 0, Fax: +49 (0) 6134 21079 24
Pharmacotherapeutic group: Anti-parkinson drugs, anticholinergic agents, biperiden
ATC code: N04AA02
Biperiden is a predominantly centrally acting anti-cholinergic. It has a peripheral effect, which is low in comparison to atropine. Biperiden binds competitively to peripheral and central muscarinic receptors (primarily M1).
In animal experiments, Biperiden influences parkinson-like conditions (tremor, rigor), which are caused by centrally acting cholinergics.
Akineton thus influences conditions, which are accompanied by cholinergic hyperactivity in the CNS: for example, Parkinson’s syndrome as extra-pyramidal dopamine deficiency syndrome as a consequence of neuronal degeneration, as well as other symptoms triggered by neuroleptics, which can likewise be attributed to a disturbance of dopaminergic neurotransmission in the basal ganglia. The balance of dopaminergic and cholinergic functions is thereby impaired. The relative cholinergic overactivity can be therapeutically suppressed by anti-cholinergic drugs, such as Akineton.
Biperiden hydrochloride is quickly absorbed after 4 mg are taken orally with a lag-time of 27min. The maximum plasma concentration of 4-7 ng/ml is attained after 1-2 h.
The bioavailability of orally administered Biperiden Hydrochloride is about 30%.
The plasma protein binding of Biperiden amounts to about 95%. An apparent distribution volume of 24 ± 4.1 l/kg was determined for Biperiden. Biperiden is easily accessible to the tissue with a half-life time of tissue distribution of 0.6 h and a ratio of the total distribution volume to central distribution volume of 9.6.
Details on the placenta passage of Biperiden are not available.
Biperiden is virtually fully metabolised – unchanged Biperiden has not been detected in the urine. The main metabolite of Biperiden occurs by hydroxylation at the bicycloheptane ring (60%), in addition an additional hydroxylation at the piperidine ring (40%) partially takes place.
The numerous metabolites (as hydroxylation products and their conjugates) are eliminated 50:50 via the urine and faeces, respectively.
The terminal plasma elimination half-life after single oral administration of Biperiden Hydrochloride in young, healthy volunteers is 11-24 h, the plasma clearance is about 146 l/kg. At steady-state, a plasma elimination half-life of 25 ± 9 h was measured.
As liver weight, blood flow and liver enzyme activity can decrease with age, a lower metabolisation rate of Biperiden in the liver can be assumed in older patients and thus an increased bioavailability and lower elimination rate in comparison to younger patients. In a comparative study, older patients showed 3-5-fold higher AUC values and 2-fold longer elimination half-lives than younger volunteers.
A terminal elimination half-life of 30 ± 6 h was determined after single oral administration in older patients. The elimination half-life time at a steady-state was 39 ± 12 h.
Pharmacokinetic data for patients with impaired liver and renal function are unknown.
Investigations on the chronic toxicity in rats and dogs gave no indication of organ toxicity.
In-vivo and in-vitro investigations with Biperiden gave no indication for a mutagenic or clastogenic effect. Long-term studies in animals regarding the tumourigenic potential of Biperiden are not available.
Biperiden has been insufficiently tested for its reproduction toxicological characteristics in animals.
No investigations are available on the effects on fertility, foetal and postnatal development. Embryo toxicity studies have given no indications of a teratogenic potential or other embryotoxic characteristics in the therapeutic dosage range.
No experience is available in humans on the safety of application during pregnancy and lactation
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