Source: Health Products and Food Branch (CA) Revision Year: 2017
Dimenhydrinate is a theoclate salt of the ethanolamine derivative diphenhydramine. The content ratio varies from 53%-55.5% for diphenhydramine, and 44%-47% for 8-chlorotheophylline. The mechanism by which dimenhydrinate exerts its antiemetic, anti-motion sickness, and antivertigo effects is not precisely known, but may possibly be related to its central anticholinergic action. Other actions may involve an effect on the medullary chemoreceptor trigger zone or dose-related inhibition of vestibular stimulation (i.e., first acting on the otolith system and in larger doses on the semicircular canals).
Dimenhydrinate is well absorbed after oral administration. Antiemetic effects occur almost immediately after IV administration, within 20-30 minutes after IM administration and 15-30 minutes after oral administration. In a study of 9 healthy volunteers given a single dose of each dosage form (separated by a washout period), Tmax and Cmax are given in the following table.
| Product | Tmax (h) | Cmax (ng/mL serum) |
|---|---|---|
| Dimenhydrinate film-coated tablets 50 mg | 2.7 | 72.6 |
| Dimenhydrinate long action capsules 75 mg | 4.0 | 68.4 |
| Dimenhydrinate suppositories 100 mg | 5.3 | 112.2 |
Serum concentrations (ng/mL) 1 and 2 hours after administration of a 50 mg dimenhydrinate tablet were: 3.65 and 3.15. While not directly applicable to dimenhydrinate, it is suggested that when plasma concentration of diphenhydramine exceeds 70 ng/mL, sleep may occur.
Dimenhydrinate, like diphenhydramine, is widely distributed into body tissues, and crosses the placenta. Small amounts of dimenhydrinate are distributed into milk. After oral administration of 4x50 mg dimenhydrinate tablets, a distribution volume of 3-4 L/kg, and protein binding of 70-85% for dimenhydrinate and 98-99% for diphenhydramine were reported. The duration of effect and therapeutic plasma level were respectively 4-6 hours and 0.1mcg/mL. The plasma elimination half-life was 5-8 hours.
Dimenhydrinate is metabolized by the liver, and excreted in urine. There are three known metabolites: diphenyl-methoxy-ethylamine, diphenyl-methoxy-acetic acid, and diphenylmethoxy-N-methylamine.
Acute toxicity was determined by administering dimenhydrinate to mice PO and IP, and in rats PO and IV. The results are shown in the following table.
| Species | Oral | IP | IV |
|---|---|---|---|
| Mice | 203 mg/kg | 110 mg/kg 149 mg/kg | -- |
| Rats | 831 mg/kg 1320 mg/kg | -- | 200 mg/kg |
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