Alfaxan Pharmacology

The pharmacokinetics of Alfaxan®

After a single dose of Alfaxan, alfaxalone is metabolized rapidly in the liver and eliminated in the bile and urine, with the drug being completely cleared from the body within a few hours after administration.29  Table 1 shows the phamacokinetic parameters of alfaxalone in both dogs and cats after a single dose administered at the clinically recommended dose rate.30

Parameter

Dog (n=8)
2 mg/kg

Cat (n=8)
5 mg/kg

Mean volume of distribution at steady state

2.0 L/kg

1.3 L/kg

Mean terminal plasma elimination half life

34 minutes

43 minutes

Mean total body clearance

59.4 mL/kg/min

24.0 mL/kg/min

The administration of Alfaxan to debilitated patients or patients with renal disease, hepatic disease or cardiorespiratory disease has not been evaluated.  Doses may need adjustment for geriatric or debilitated patients.  Caution should be used in cats or dogs with cardiac, respiratory, renal or hepatic impairment, or in hypovolemic or debilitated cats and dogs and geriatric animals.

Anesthesia

After intravenous (IV) administration of Alfaxan the duration of unconsciousness seen in patients will vary depending on the patient’s physical state, concurrent medications and the dose of Alfaxan administered.  As a general guide, with no noxious stimuli, healthy un-premedicated cats administered a 5 mg/kg dose of Alfaxan IV will remain anesthetized for approximately 25 minutes19 and healthy unpremedicated dogs administered 2 mg/kg of Alfaxan IV will remain anesthetized for approximately 10 minutes.20
If required, anesthesia may be prolonged by administration of maintenance gaseous agents (such as isoflurane) or further administration of Alfaxan.  Concurrent sedative and analgesic medications can be expected to decrease the dose requirements for Alfaxan and alter the duration of resulting anesthesia.

Cardiorespiratory profile

Effect on blood pressure – Patients induced with Alfaxan generally maintain clinically acceptable blood pressure parameters.31, 32

Mean of observed systolic blood pressures by anesthetic period

(Canine Multisite clinical trial 31)

Mean of observed systolic blood pressures by anesthetic period

(Feline Multisite clinical trial32)

The myocardial depressive effects of Alfaxan combined with the vasodilatory effects of inhalant anesthetics can be additive, resulting in hypotension. Preanesthetics may increase the anesthesia effect of Alfaxan and result in more pronounced changes in systolic, diastolic and mean arterial blood pressures. Transient hypertension may occur, possibly due to elevated sympathetic activity.

Cardiorespiratory profile

effect on respiratory rate

Mean of observed respiratory rates by anesthetic period

(Canine Multisite clinical trial31) 

Mean of observed respiratory rates by anesthetic period

(Feline Multisite clinical trial32)

Patients that are anesthetized with Alfaxan generally breathe spontaneously and maintain clinically acceptable respiratory rates.31, 32

Apnea may occur following administration of an induction dose, a maintenance dose or a dose administered during the transition to inhalant maintenance anesthesia, especially with higher doses and rapid administration.  Endotracheal intubation, oxygen supplementation and intermittent positive pressure ventilation (IPPV) should be administered to treat apnea and associated hypoxemia.