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Biperiden

Brand names: AKINETON

Mechanism of Action

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).

Pharmacodynamic Properties

In animal experiments, Biperiden influences parkinson-like conditions (tremor, rigor), which are caused by centrally acting cholinergics.

Biperiden 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 over-activity can be therapeutically suppressed by anti-cholinergic drugs, such as biperiden.

Pharmacokinetic Properties

Absorption

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.

Bioavailability

The bioavailability of orally administered Biperiden Hydrochloride is about 30%.

Distribution

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.

Biotransformation

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.

Elimination

The terminal plasma elimination half-life after single administration of an injection of biperiden Lactate to young, healthy volunteers is around 24 h; the plasma clearance is 11.6 ml/min/kg.

Older patients

Bioavailability and elimination

As liver weight, blood flow and liver enzyme activity can decrease with age, a lower metabolisation rate of biperiden in the liver is to 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.

Pharmacokinetic data for patients with impaired liver and renal function are unknown.

Preclinical Safety Data

Chronic toxicity

Investigations on the chronic toxicity in rats and dogs gave no indication of organ toxicity.

Mutagenic and tumourigenic potential

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.

Reproduction toxicity

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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