Pharmacokinetics of trihexyphenidyl after short‐term and long‐term administration to dystonic patients

Abstract

Although trihexyphenidyl has been used effectively for many years in the treatment of Parkinson's disease, little is known about its pharmacokinetics. Using a sensitive radioreceptor assay for anticholinergic drugs, we assayed trihexyphenidyl in human serum and studied its pharmacokinetics following short-term and long-term administration to patients with dystonia. Previously untreated patients had a biphasic semilogarithmic plot of serum concentration-time consisting of an initial rapid distribution phase and a later slower elimination phase. Patients on long-term treatment showed only the slower elimination phase. Elimination followed first-order kinetics and was rapid, with a half-life of 3.7 +/- 0.4 (SEM) hours. There was no relationship between half-life and peak serum level, age, duration of therapy, or etiology or severity of dystonia. Although acute anticholinergic side effects paralleled the rise and fall of serum anticholinergic levels, the response of dystonia did not.

Clinical Pharmacokinetics of Anti-Parkinsonian Drugs

“…The disappearance of benzhexol from the blood appears consistent with a 2-compartment model with the terminal elimination phase following first-order kinetics. Following oral dosing, Burke and Fahn (1985b) found a biphasic decline in plasma concentrations, with an initial phase half-life of 1.3 ± 0.3 hours and a terminal half-life of 5.6 ± 1.6 hours with acute treatment and a monophasic decline with a half-life of 3.2 ± 0.3 hours in chronically treated dystonia patients. The more specific GLC assay method yielded an elimination half-life of 10.2 ± 4.7 hours (Tynan, personal communication), suggesting that inactive metabolites could have interfered with the radioreceptor method.…”

“…Peak serum concentrations of benzhexol are reached within 1 to 1.3 hours of oral administration (Burke & Fahn 1985b; Tynan, personal communication) regardless of age of subject, size of dose or diagnosis. Peak concentrations of approximately 80 IJ.g/L were obtained following single oral doses of benzhexol 10mg either as tablets, capsules or liquid suspension (Tynan, personal communication).…”

Treatment strategies for dystonia

“…Eye drops and oral pyridostigmine can be used to combat peripheral side effects. Acute anticholinergic side effects parallel the rise and fall of serum drug levels, but the therapeutic response of dystonia does not [11]. Acute narrow-angle glaucoma is the only absolute contraindication to its use, although there are several relative contraindications including urinary hesitancy and dementia.…”

Effects of trihexyphenidyl and L-dopa on brain muscarinic cholinergic receptor binding measured by positron emission tomography

“…Trihexyphenidyl (Artane) is one of the most popular and efficacious drugs in the anticholinergic class (Obeso and Martinez-Lage, 1987). However, little is known about the pharmacokinetics of trihexyphenidyl because an adequate assay has not been developed for its measurement (Burke and Fahn, 1982;Obeso and Martinez-Lage, 1987).…”