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Mechanism of Action
The mechanism of action of Tigan (trimethobenzamide hydrochloride capsules) as determined in animals is obscure, but may involve the chemoreceptor trigger zone (CTZ), an area in the medulla oblongata through which emetic impulses are conveyed to the vomiting center; direct impulses to the vomiting center apparently are not similarly inhibited. In dogs pretreated with trimethobenzamide HCl, the emetic response to apomorphine is inhibited, while little or no protection is afforded against emesis induced by intragastric copper sulfate.
The pharmacokinetics of trimethobenzamide have been studied in healthy adult subjects. Following administration of 200 mg (100 mg/mL) Tigan (trimethobenzamide hydrochloride capsules) I.M. injection, the time to reach maximum plasma concentration (Tmax) was about half an hour, about 15 minutes longer for Tigan (trimethobenzamide hydrochloride capsules) 300 mg oral capsule than an I.M. injection. A single dose of Tigan (trimethobenzamide hydrochloride capsules) 300 mg oral capsule provided a plasma concentration profile of trimethobenzamide similar to Tigan (trimethobenzamide hydrochloride capsules) 200 mg I.M. The relative bioavailability of the capsule formulation compared to the solution is 100%. The mean elimination half-life of trimethobenzamide is 7 to 9 hours. Between 30 – 50% of a single dose in humans is excreted unchanged in the urine within 48-72 hours. The major pathway of trimethobenzamide metabolism is through oxidation resulting in the formation of trimethobenzamide N-oxide metabolite. The pharmacologic activity of this major metabolite has not been evaluated.
The clearance of trimethobenzamide is not known in patients with renal impairment. However, it may be advisable to consider reduction in the dosing of trimethobenzamide in elderly patients with renal impairment considering that a substantial amount of excretion and elimination of trimethobenzamide occurs via the kidney and that elderly patients may have various degrees of renal impairment. (See PRECAUTIONS: General and DOSAGE AND ADMINISTRATION).
Systemic exposure to trimethobenzamide was similar between men (N=40) and women (N=28).
Pharmacokinetics appeared to be similar for Caucasians (N=53) and African Americans (N=12).
The clearance of trimethobenzamide is not known in patients with renal impairment. However, it may be advisable to consider reduction in the dosing of trimethobenzamide in patients with renal impairment considering that a substantial amount of excretion and elimination of trimethobenzamide occurs via the kidney. (See PRECAUTIONS: General and DOSAGE AND ADMINISTRATION).
Last reviewed on RxList: 1/23/2009
This monograph has been modified to include the generic and brand name in many instances.
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