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

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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.

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