Anticholinergic drugs used in Parkinson's disease: An overlooked class of drugs from a pharmacokinetic perspective.

Anticholinergic drugs were the first pharmacological agents used in the tre atment of Parkinson's disease. Although levodopa and other centrally acting dopaminergic agonists have largely supplanted their use, they still have a place in treatment of the disease. As a therapeutic class, there is little pharmacokinetic information available for these drugs, which is inclusive of benztropine, biperiden, diphenhydramine, ethopropazine, orphenadrine, pr ocyclidine and trihexyphenidyl. Pharmacokinetic information is largely rest ricted to studies involving young health volunteers given single doses. In general, this class of drugs is rapidly absorbed after oral administration to humans. Oral bioavailability is variable between the different drugs, ra nging from 30% to over 70%. Each of the drugs appears to possess a large Vd in humans and animals, and distribution to tissues is rapid. The drugs are all characterized by relatively low clearance relative to hepatic blood fl ow, and appear to be extensively metabolized, primarily to N-dealkylated an d hydroxylated metabolites. The available information suggests that excreti on of parent drug and metabolite is via the urine and bile. Although the ex istence of a plasma concentration vs. therapeutic effect relationship has n ot been explored, there is some evidence suggesting a relationship between concentration and peripheral side effects. Elderly tolerate the drugs less well than do younger patients. There is a notable lack of pharmacokinetic i nformation for these drugs in the elderly. The lack of pharmacokinetic info rmation for multiple dose administration and in the elderly may be a possib le hindrance in the safe and effective use of these drugs in patients with Parkinson's disease.