KETAMINE HYDROCHLORIDE INJECTION USP FOR INTRAVENOUS, INTRAMUSCULAR USE

Product Information

Registration Status: Active

KETAMINE HYDROCHLORIDE INJECTION USP is approved to be sold in Singapore with effective from 1991-05-23. It is marketed by DUOPHARMA (SINGAPORE) PTE LTD, with the registration number of SIN05966P.

This product contains Ketamine 50mg/ml in the form of INJECTION. It is approved for INTRAVENOUS, INTRAMUSCULAR use.

This product is manufactured by ROTEXMEDICA GMBH in GERMANY.

It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.

Description

Ketamine is an NMDA receptor antagonist with a potent anesthetic effect.[A31869] It was developed in 1963 as a replacement for phencyclidine (PCP) by Calvin Stevens at Parke Davis Laboratories. It started being used for veterinary purposes in Belgium and in 1964 was proven that compared to PCP, it produced minor hallucinogenic effects and shorter psychotomimetic effects. It was FDA approved in 1970, and from there, it has been used as an anesthetic for children or patients undergoing minor surgeries but mainly for veterinary purposes.[L1332]

Indication

Ketamine is indicated as an anesthetic agent for recommended diagnostic and surgical procedures. If skeletal muscle relaxation is needed, it should be combined with a muscle relaxant. If the surgical procedure involves visceral pain, it should be supplemented with an agent that obtunds visceral pain. Ketamine can be used for induction of anesthesia prior other general anesthetic agents and as a supplement of low potency agents.[L1336, FDA label] Reports have indicated a potential use of ketamine as a therapeutic tool for the management of depression when administered in lower doses.[A31873] These reports have increased the interest for ketamine in this area and several clinical trials are launched for this indication.[L1337, A31874]

Mechanism of Action

Ketamine interacts with N-methyl-D-aspartate (NMDA) receptors, opioid receptors, monoaminergic receptors, muscarinic receptors and voltage sensitive Ca ion channels. Unlike other general anaesthetic agents, ketamine does not interact with GABA receptors.[A2187]

Pharmacokinetics

Absorption: Ketamine absorption is very rapid and the bioavailability is around 93%. After the first pass metabolism, only 17% of the administered dose is absorbed.[A31883] It distributes very rapidly and presents a distribution half-life of 1.95 min.[A31887] The Cmax levels at peak reach 0.75 mcg/ml in plasma and 0.2 mcg/ml in cerebrospinal fluid.[L1336]
Distribution: The apparent volume of distribution of the central compartment and at steady-state are 371.3 ml/kg and 4060.3 ml/kg, respectively.[A31889]
Metabolism: Ketamine presents a mainly hepatic metabolism and its major metabolite is norketamine. The biotransformation of ketamine corresponds to N-dealkylation, hydroxylation of the cyclohexone ring, conjugation to glucuronic acid and dehydration of the hydroxylated metabolites for the formation of cyclohexene derivatives.[A31883]
Elimination

Clearance

The clearance rate of ketamine is high and of around 95 L/h/70kg.[A31885]

Toxicity

Preclinical studies related to the blocking of NMDA receptors have shown an increase in apoptosis in the developing brain which results in cognitive deficits when used for longer than 3 hours. Toxicity studies regarding carcinogenesis have not been performed. Regarding mutagenesis and fertility, ketamine showed to be clastogenic and to not have effects on fertility.[FDA label]

Active Ingredient/Synonyms

Source of information: Drugbank (External Link). Last updated on: 3^rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.