FARMACOCINTICA Y FARMACODINAMIA: El biperideno es un anticolinrgico con accin preferente sobre el sistema nervioso central ms que en el sistema nervioso perifrico,

por lo que sus efectos vegetativos perifricos son ms dbiles que los de la atropina. El mecanismo de accin de la actividad anticolinrgica central del biperideno se produce por un antagonismo competitivo contra la acetilcolina por los receptores colinrgicos en varias estructuras cerebrales, pero en especial en el cuerpo estriado y sustancia nigra. Biperideno posee adems una marcada accin nicotinoltica, por antagonismo competitivo sobre los receptores nicotnicos. En humanos, biperideno se absorbe bien en el tracto gastrointestinal, hasta 87% de la dosis administrada y tras una dosis nica de 4 mg por va oral, se logran concentraciones plasmticas entre 4 y 5 ng/ml, 1.5 horas despus de su administracin; sufre hidroxilacin heptica y no se han reportado metabolitos activos; se elimina principalmente por las heces y por la orina, y 48 horas despus de una sola administracin, slo se detectan concentraciones plasmticas entre 0.1 y 0.2 ng/ml.
Biomed Chromatogr. 2002 Feb;16(1):47-55.

The determination of biperiden in plasma using gas chromatography mass spectrometry: pharmacokinetics after intramuscular administration to guinea pigs.
Capacio BR, Caro ST, Smith JR, Byers CE.

Source
Pharmacology Division, US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, MD 21010-5400, USA. benedict.capacio@amedd.army.mil

Abstract
A gas chromatographic-mass spectrometric (GC-MS) method has been developed for the analysis of the biperiden from plasma. The method utilizes 290 microl of plasma and a simple hexane extraction/clean-up procedure. Standard curves were linear over the range of 1.9-250 ng/mL. The range of correlation coefficients for the individual standard curves was 0.9984-0.9999; the largest coefficient of variation expressed as a percentage (% CV) was 11.5%. Precision and accuracy were examined by assessing between-day and within-day variability. For between-day precision, the % CVs ranged from 2.86 to 5.17%. Accuracy as expressed by percentage error ranging from -2.16 to 5.83%. The study for within-day precision demonstrated % CVs from 0.95 to 5.55% with accuracy from -3.37 to 2.45%. Applicability of the method was demonstrated by examining the pharmacokinetics of intramuscular (i.m.) biperiden as an anticonvulsant treatment in a guinea pig model for organophosphate (OP)-induced seizure activity. Mean pharmacokinetic parameter estimates were similar to literature values; selected mean pharmacokinetic parameter estimates were: apparent volume of distribution, 13.9 L/kg; half-life of elimination, 93 min; time to maximal plasma concentration, 27.4 min; and maximal plasma concentration, 32.22 eta g/mL. The time to maximal plasma concentration was found to be similar to the onset time for terminating OP-induced seizure activity in guinea pigs receiving biperiden as an anticonvulsant treatment. The studies indicate that the method affords the required precision, accuracy and sensitivity to assay biperiden at the doses utilized for these pharmacokinetic studies after i.m. administration to guinea pigs. Copyright 2001 John Wiley & Sons, Ltd. Abbreviations used: AChE Acetylcholinesterase AUC area under the curve OP organophosphate 2PAM pralidoxime chloride PYR pyridostigmine

Biperiden
Pharmacokinetics

Absorption

29% bioavailable; C

max

is 4 to 5 mcg/L; T

max

is 1 to 1.5 h.

Elimination
The t

is 18.4 to 24.3 h.

Most cited papers:

Eur J Clin Pharmacol. 1984 ;27 (5):619-21 6519170 Cit:13

Biperiden effects and plasma levels in volunteers.

M Hollmann, E Brode, G Greger, H Mller-Peltzer, N Wetzelsberger

The pharmacokinetics of biperiden was studied and compared with pharmacodynamics (pupil size, accommodation, self-rating mood scale) in 6 healthy volunteers. A single-blind cross-over design was employed with placebo and biperiden (4 mg as commercially available tablets). After a lag time of 0.5 h, biperiden was rapidly absorbed with a half-life of 0.3 h, plasma peak levels of 5 ng/ml being reached after 1.5 h. Biperiden showed good tissue penetration (distribution half-life 0.6 h; ratio of total to central distribution volume 9.6), the terminal half-life time of plasma concentration was 18 h, and the oral clearance was 146 l/h. The pharmacodynamic maximum lagged behind the plasma peak concentration by 1 (self-rating) to 4 h (accommodation).
J Pharm Sci. 1987 Jan ;76 (1):10-3 3585715 Cit:13

Effects of fasting on biperiden pharmacokinetics in the rat.

E Nakashima, K Yokogawa, F Ichimura, T Hashimoto, T Yamana, A Tsuji

The effects of fasting on the pharmacokinetics of biperiden in rats were examined. Total clearance of biperiden was greater than 90% ascribable to hepatic clearance and was essentially blood-flow dependent. The number of compartments in the preferred pharmacokinetic model of biperiden changed from three (for normal rats) to two (for fasted rats). The smaller mean residence time (MRT) values found for fasted rats were attributable to decreases in distribution volume. Biperiden showed much higher lipophilicity than haloperidol, thiopental, and hexobarbital, and its tissue-to-plasma partition coefficient in adipose tissue was 20-fold higher than that in muscle. The influence of changes in volumes of adipose tissue and muscle on distribution volume (Vdss/BW) was evaluated from tissue-to-plasma partition coefficients. The value of Vdss/BW was predicted to decrease with decrease of adipose tissue, and to increase with decrease of muscle tissue. These results suggest that the observed decrease of Vdss/BW in fasted rats reflects reduced capacity to trap biperiden in the body, especially in adipose tissue. Possible clinical implications of these results are discussed.
Eur J Clin Pharmacol. 1986 ;29 (6):735-7 3709619 Cit:10

Pharmacokinetic and pharmacodynamic studies following the intravenous and oral administration of the antiparkinsonian drug biperiden to normal subjects.
R Grimaldi, E Perucca, G Ruberto, C Gelmi, F Trimarchi, M Hollmann, A Crema

The pharmacokinetics and pharmacodynamics (changes in pupil size and salivary flow) of biperiden following a single oral and intravenous dose were investigated in six normal subjects. After the injection plasma concentrations declined biphasically, with halftimes of 1.5 h for the rapid phase and 24 h for the terminal phase. Clearance and apparent volume of distribution were high (12 ml X min-1 X kg-1 and 24 l X kg-1 respectively). Absorption was rapid but the systemic availability was incomplete (33%), probably due to first-pass metabolism. Central nervous system (CNS) adverse effects and changes in pupil size were observed after both routes of administration while salivary flow was affected only by the injection.