Monograph

N01AB06 - Isoflurane

Propably not porphyrinogenic

Rationale

Isoflurane has a low hepatic metabolism, it is not metabolised by the most abundant CYP isoenzymes, 3A4 and 2C9. Probably insignificant metabolism by CYP 2E1. Possible inducer of hepatic CYP 2B6. There are both preclinical and clinical experience pointing to non-porphyrogenicity.

Chemical description

1-Chloro-2,2,2-trifluoroethyl difluoromethyl ether; 2-Chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane. M= 184.5. Halogenated ethyl methylether used in inhalation anesthesia, isomer to enflurane. Volatile, boiling point of 48 degree celcius.

Therapeutic characteristics

Inhalation anestethic. It is used in the induction and maintenance of general anaesthesia although induction is more often carried out using an intravenous anaesthetic. Isoflurane is also used in subanaesthetic doses to provide analgesia in obstetrics and other painful procedures.

Hepatic exposure

As for all inhalation anesthetics the hepatic exposure will be sufficient enough to affect the porphyria status of the patient.

Metabolism and pharmacokinetics

About 95% is eliminated by the lungs. About 0.2% of inhaled isoflurane is metabolised, mainly to inorganic fluoride. Isoflurane is metabolised by the 2B6 and 2E1 isoforms, it is an activator for the 2B6 isoform.

Preclinical data

Isoflurane causes no increase in ALAS activity in rats (Parikh, et al. 1978).

Personal communication

In Sweden it is repeatedly observed not to cause porphyric side effects.

Published experience

There are several reports of safe use of isoflurane in patients with porphyria. (Kantor G, et al. 1992),(Lin YC, et al. 1990),(McLouglin C 1989).

IPNet drug reports

Uneventful use reported in 1 patient with acute porphyria.

References

#	Citation details	PMID
*	Scientific articles
1.	Leitlinie zur durchführung von anästhesien bei patienten mit porphyrie. Anästhesiologie & intensivmedizin 2002;43:485-9. Böhrer H, et al.
2.	Acute intermittent porphyria and caesarean delivery. Kantor G, et al. Can J Anaesth. 1992;39(3):282-5.	1551161
3.	Atracurium in a patient with acute intermittent porphyria. Lin YC, et al. Anesth Analg. 1990;71(4):440-1.
4.	Use of propofol in a patient with porphyria. McLouglin C. Br J Anaesth. 1989;62(1):114.
5.	Effect of certain anaesthetic agents on the activity of rat hepatic delta-aminolaevulinate synthase. Br J Anaesth 1978;50:1099-1103. Parikh RK, et al.	718778
6.	Summary of information on human CYP enzymes: Human p450 metabolism data. Rendic S. Drug Metab Rev. 2002;34(1-2):83-448.	11996015
*	Drug reference publications
7.	Sweetman S (ed), Martindale: The Complete drug reference. Isoflurane Monography. London: Pharmaceutical Press. Electronic version. (read 27. may 2008).

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