[Pharmacokinetics (rats and rabbits) of N-methyl-4- piperidinylbenzilate (Po)3]

Plasma concentrations of the anticholinergic diphenylmethane derivative N-methyl-4-piperidinylbenzilate (Po;1) in rats after i.v. and p.o. administration of the drug and in 6 rabbits after i.v. administration of the drug were estimated by a gc capillary column technique in connection with detection by thermoionisation. Furthermore, after i.v. administration of the drug its concentrations in different tissues (heart, lung, liver, kidneys and brain) were estimated in rats. The results show a fast absorption of the drug after p.o. administration and also a fast decrease of 1 plasma concentrations in all plasma concentration curves obtained indicating a fast distribution of 1 in deeper tissue compartments. A high affinity especially to the lung and the heart can be derivated from the high 1 tissue concentrations in the rat. A common feature of all 1 plasma concentration curves obtained is the repeated appearance of concentration peaks which is particularly marked in the individual 1 plasma curves at the rabbits. We observed great interindividual differences in the pharmacokinetic behaviour. Furthermore, some plasma concentrations are below the detection limit of the analytical method used. These are the reasons why curve fitting to usual pharmacokinetic compartment models and the determination of parameters i.e. AUC and MRT is not suitable. However, the results agree with the assumption of a multi-compartment model at which the drug is periodical released in the general circulation. Interactions with biological membranes resulting out of the amphiphily of the drug are some possible reasons for the outstanding pharmacokinetic behaviour.