LAAM-Pharmacology and Pharmacokinetics,Developmental History,and Therapeutic Considerations

Abstract

LAAM (levo-α-acetylmethadol; methadyl acetate) was approved by the Food and Drug Administration on July 9, 1993, as a treatment for opioid dependence. It is a synthetic μ-opioid agonist that produces pharmacodynamic effects qualitatively similar to methadone. LAAM can produce a competitive blockade of the effects of other opioids and can suppress opioid-withdrawal signs and symptoms. However, unlike methadone, LAAM may be administered on an alternate-day or three-times-weekly dosing schedule due to its long duration of action and that of its pharmacologically active metabolites. LAAM provides clinicians and patients with a pharmacotherapeutic alternative to methadone when opioid-substitution therapy is indicated.

Keywords

methadyl acetaten opiate dependence pharmacotherapy opiate substitution

Get full access to this article

View all access options for this article.

References

Roxane Laboratories, Inc. 1995. ORLAAM Product Labeling Columbus, OH

Fraser

H F

and Isbell

. 1952. Actions and addiction liabilities of alpha-acetylmethadols in man. J Pharmacol Exp Ther, 105: 458–465.

Fraser

H F

, Nash

T L

, Vanhorn

G D

and Isbell

. 1954. Use of miotic effect in evaluating analgesic drugs in man. Arch Int Pharmacodyn Ther, 98: 443–451.

Inturrisi

C E

and Verebely

. 1972. The levels of methadone in the plasma in methadone maintenance. Clin Pharmacol Ther, 13: 633–637.

Sawe

. 1986. High-dose morphine and methadone in cancer patients. Clinical pharmacokinetic considerations of oral treatment. Clin Pharmacokinet, 11: 87–106.

Inturrisi

C E

, Colburn

W A

, Kaiko

R F

, Houde

R W

and Foley

K M

. 1987. Pharmacokinetics and pharmacodynamics of methadone in patients with chronic pain. Clin Pharmacol Ther, 41: 392–401.

Sullivan

H R

and Due

S L

. 1973. Urinary metabolites of d/-methadone in maintenance subjects. J Med Chem, 16: 909–913.

McMahon

R E

, Calp

H W

and Marshal

F J

. 1965. The metabolism of alpha-d/-acetyl methadol in the rat: The identification of a probable active metabolite. J Pharmacol Exp Ther, 149: 436–445.

Billings

R E

, Booker

, Smits

, Pehland

and McMahon

R E

. 1973. Metabolism of acetyl methadol. A sensitive assay for nor acetyl methadol and the identification of a new active metabolite. J Med Chem, 16: 305–306.

10.

Nickander

, Booher

and Miles

. 1974. Alpha-l-acetylmethadol and its N-demethylated metabolites have potent opiate action in the guinea pig isolated ileum. Life Sci., 14: 2011–2017.

11.

Henderson

G L

, Wilson

B K

and Lau

D HM

. 1977. Plasma l-alpha-acetylmethadol (LAAM) after acute and chronic administration. Clin Pharmacol Ther, 2: 16–25.

12.

Levine

, Zaks

, Fink

and Freedman

A M

. 1973. Levomethadyl acetate: Prolonged duration of opioid effects, including cross tolerance to heroin, in man. JAMA, 226: 316–318.

13.

Chen

K K

. 1948. Pharmacology of methadone and related compounds. Ann NY Acad Sci., 51: 83–97.

14.

Keats

A S

and Beecher

H K

. 1952. Analgesic activity and toxic effects of acetylmethadol isomers in man. J Pharmacol Exp Ther, 105: 210–215.

15.

David

N A

, Semler

H J

and Burgner

P R

. 1956. Control of chronic pain by dl-alpha-acetylmethadol. JAMA, 161: 599–603.

16.

Dole

V P

and Nyswander

. 1965. A medical treatment for diacetylmorphine (heroin) addiction: A clinical trial with methadone hydrochloride. JAMA, 193: 80–84.

17.

Blaine

J D

, Thomas

D B

, Barnett

, Whysner

J A

and Renault

P F

. 1981. “Levo-alpha-acetylmethadol (LAAM): Clinical utility and pharmaceutical development”. In Substance Abuse: Clinical Problems and Perspectives, Edited by: Lowinson

J H

and Ruiz

. 360–388. Baltimore: Williams and Wilkins.

18.

Jaffe

J H

, Schuster

C R

, Smith

B B

and Blachly

P H

. 1970. Comparison of acetylmethadol and methadone in the treatment of long-term heroin users. A pilot study. JAMA, 211: 1834–1836.

19.

Jaffe

J H

and Senay

E C

. 1971. Methadone and l-methadylacetate. Use in management of narcotics addicts. JAMA, 216: 1303–1305.

20.

Jaffe

J H

, Senay

E C

, Schuster

C R

, Renault

P R

, Smith

and Di Menza

. 1972. Methadyl acetate vs methadone. A double-blind study in heroin users. JAMA, 222: 437–442.

21.

Savage

, Karp

and Curran

. 1976. A methadone/alpha-acetylmethadol (LAAM) maintenance study. Comp Psychiatry, 17: 415–424.

22.

Senay

E C

, Dorus

and Renault

P F

. 1977. Methadyl acetate and methadone, an open comparison. JAMA, 237: 138–142.

23.

Judson

B A

and Goldstein

. 1979. Levo-alpha-acetylmethadol (LAAM) in the treatment of heroin addicts. I. Dosage schedule for induction and stabilization. Drug Alcohol Depend, 4: 461–466.

24.

Freedman

R R

and Czertko

. 1981. A comparison of thrice weekly LAAM and daily methadone in employed heroin addicts. Drug Alcohol Depend, 8: 215–222.

25.

Blaine

J D

and Renault

P F

. 1976. Rx: 3x/week LAAM, Alternative to methadone, 1–9. Rockville, MD: Department of Health, Education, and Welfare. Introduction. NIDA Research Monograph 8

26.

Ling

, Charuvastra

V C

, Kaim

S C

and Klett

C J

. 1976. Methadyl acetate and methadone as maintenance treatments for heroin addicts. Arch Gen Psychiatry, 33: 709–720.

27.

Ling

, Klett

C J

and Gillis

R D

. 1978. A cooperative clinical study of methadyl acetate. Arch Gen Psychiatry, 35: 345–353.

28.

Finkel

M J

. 1984. The Orphan Drug Act and the federal government's orphan products development program. Public Health Rep, 99: 313–316.

29.

Fudala

P J

, Montgomery

, Herbert

, Mojsiak

, Rosenberg

and Vocci

. 1994. A multicenter, labelling assessment study of levo-alpha-acetylmethadol (LAAM) for the maintenance treatment of opiate addicts, 145Rockville, MD: Department of Health and Human Services. NIDA Research Monograph 141

30.

Kampman

, Bartzokis

, Lange

W R

, Nuite-Belleville

J A

, Nademanee

, Beckson

, Charuvastra

, Wilkins

, Yu

and Fudala

P J

. 1994. An evaluation of the effects of levo-alpha-acetylmethadol (LAAM) on the human electrocardiogram, 381Rockville, MD: Department of Health and Human Services. NIDA Research Monograph 141

31.

Beckson

, Ling

, Vocci

, Pickworth

, Fudala

, Wilkins

and Clagett-Carr

. Pharmacokinetic studies of LAAM: Clinical correlates, Rockville, MD: Department of Health and Human Services. (in press) NIDA Research Monograph

32.

Herbert

, Montgomery

, Fudala

, Vocci

, Gampel

, Mojsiak

, Hill

and Walsh

. LAAM labeling assessment study: Retention, dosing, and side effects in a 64-week study, Rockville, MD: Department of Health and Human Services. NIDA Research Monograph (in press)

33.

Nightingale

S L

. 1993. Levomethadyl approved for the treatment of opiate dependence. JAMA, 270: 1290

34.

Resnick

R B

. 1977. Problems of methadone diversion and implications for control. Int J Addict, 12: 803–806.

35.

Goldman

F R

and Thistel

C I

. 1978. Diversion of methadone: Illicit methadone use among applicants to two metropolitan drug abuse programs. Int J Addict, 13: 855–862.

36.

Food and Drug Administration. 1993. Levo-alpha-acetylmethadol (LAAM) in maintenance: Revision of conditions for use in the treatment of narcotic addiction. Fed Register, 58(137): 38704–38711.

37.

Kreek

M J

, Gutjahr

C L

, Garfield

J W

, Bowen

D V

and Field

F H

. 1976. Drug interactions with methadone. Ann NY Acad Sci., 281: 35–371.

38.

Parke

D V

, Ioannides

and Lewis

D FV

. 1991. The role of the cytochromes P450 in the detoxification and activation of drugs and other chemicals. Can J Physiol Pharmacol, 69: 537–549.