Cyclobenzaprine Pharmacokinetics, Including the Effects of Age, Gender, and Hepatic Insufficiency

Abstract

The pharmacokinetics and bioavailability of cyclobenzaprine, a widely used muscle relaxant, were investigated in four clinical studies, and the effects of age, gender, and hepatic insufficiency were characterized. Cyclobenzaprine plasma clearance was 689 ml/min, and the bioavailability of a 5 mg oral dose was 0.55. Following oral doses of 2.5 to 10 mg tid in healthy young subjects, cyclobenzaprine pharmacokinetics were linear, and plasma concentrations generally increased proportional to dose. There was about a fourfold accumulation of the drug in plasma on multiple dosing, corresponding to an effective half-life of 18 hours. Steady-state plasma concentrations of cyclobenzaprine in elderly subjects were twice as high as in young subjects following oral doses of 5 mg tid. Steady-state plasma concentration also appeared to be up to twofold higher in subjects with mild hepatic insufficiency compared to healthy controls. The magnitude of any difference in steady-state plasma concentration between males and females appears to be small relative to intersubject variability. A reduction in dose or dosing frequency should be considered in the elderly and in patients with liver disease.

Torticollis under Cyclobenzaprine

“…The close temporal association strongly suggests that the dystonic symptoms were caused by cyclobenzaprine. The effective half-life of cyclobenzaprine is 18 h [10] , and after 4 days steady state is reached which equals the period of time during which cyclobenzaprine had been given.…”

Pharmacokinetics and Bioequivalence Evaluation of Cyclobenzaprine Tablets

“…After 10 mg immediate-release tablet oral administration, cyclobenzaprine is absorbed with estimates of mean bioavailability ranging from 33% to 55% [9–11]. Approximately 93% of the drug is bound to plasma proteins [12].…”

Comparative Bioavailability and Pharmacodynamic Aspects of Cyclobenzaprine and Caffeine in Healthy Subjects and the Effect on Drowsiness Intensity

“…Cyclobenzaprine hydrochloride is a centrally acting muscle relaxant that has been widely used over the past 30 years for relief of muscle spasm associated with acute, painful musculoskeletal conditions (Borenstein et al, 2003;Browning et al, 2001; Katz et al, 1988;Winchell et al, 2002). Disposition studies in humans and laboratory animals have previously shown that cyclobenzaprine hydrochloride is well absorbed (Hucker et al, 1978), is widely distributed among body tissues (Hucker et al, 1978), is subject to enterohepatic circulation (Wang et al, 1996), and is extensively metabolized via both oxidative and conjugative pathways (Hucker et al, 1978).…”

“…Cyclobenzaprine pharmacokinetics are linear for doses from 2.5 to 10 mg despite the slight deviations from linearity observed at the 5 mg dose (Winchell et al, 2002). Like other tricyclic antidepressants, cyclobenzaprine is also prescribed off-label as a sleep-aid.…”