Evidence for route dependent biotransformation of cyclobenzaprine hydrochloride.

Cyclobenzaprine hydrochloride was administered to healthy volunteers as a 10 mg oral tablet, 10 mg and 20 mg intramuscular injections, and a 10 mg intravenous injection. Urinary excretion and plasma level data for cyclobenzaprine together provide evidence for route dependent biotransformation. Urinary excretion of total cyclobenzaprine (unchanged plus the glucuronide conjugate) was greater for the oral treatment than for the parenteral treatments (i.m. and i.v.). Area under the plasma concentration-time curve for unchanged cyclobenzaprine, however, was less for the oral treatment than for the parenteral treatments. Based on area calculations, the bioavailability of the 10 mg oral tablet, 10 mg i.m. and 20 mg i.m. injection was 0.33, 0.76, and 0.56, respectively, when compared to the 10 mg i.v. injection of cyclobenzaprine hydrochloride. The four treatments were well tolerated and no clinically adverse effects were observed.