      Document 0141
 DOCN  DRG0141
 UNIQUE IDENTIFIER        DRG-0106
 NAME OF SUBSTANCE        MTP-PE/MF59 [Int Conf AIDS 1992 Jul
                          19-24;8(2):(abstract no. PoA 2226)]
 STANDARD CHEMICAL NAME   L-Alaninamide,
                          N-(N-acetylmuramoyl)-L-alanyl-D-alpha-glutami-
                          nyl-N-
                          (4-hydroxy-10--oxo-7((1-oxohexadecyl)oxy)-3,5-
                          ,9- trioxa-4-phosphapen tacos-1-yl)--,
                          P-oxide, (R)- [CHEMLINE]
 SYNONYMS                 Muramyl tripeptide phosphatidylethanolamine
                          [CHEMLINE]
 SYNONYMS                 Muramyl tripeptide PE [CHEMLINE]
 SYNONYMS                 Muramyl
                          tripeptide-1,2-dipalmitoylphosphatidylethanol-
                          amine conjugate [CHEMLINE]
 SYNONYMS                 Muramyl tripeptide [AmFAR Tx Dir 1993;6(4)]
 PROTOCOL ID NUMBERS      NIAID VEU 005A/B
 PROTOCOL ID NUMBERS      NIAID VEU 103
 PROTOCOL ID NUMBERS      NIAID VEU 007A/B
 PROTOCOL ID NUMBERS      NIAID VEU 015
 SECONDARY SOURCE ID      CGP 19 835A [NIAID VEU 005]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: A biological response
                          modifier, with immunomodulating activities,
                          that is believed to act by the mechanism of
                          macrophage-monocyte activation. Used as an
                          adjuvant or substance that augments the
                          immune response to vaccines. A recent trial
                          combining ENV 2-3/MTP-PE/MF59 showed this
                          combination of virus and adjuvant emulsion is
                          reactogenic and stimulates high rates of
                          serum antibody responses as detected by WB
                          and ELISA. [Int Conf AIDS 1992 Jul
                          19-24;8(2):(abstract no. PoA 2226)] [NIAID
                          VEU 005]
 DISEASES STUDIED/TREATED Primary HIV infection - enhancement of immune
                          response [AmFAR Tx Dir 1993;6(4)]
 CLASSIFICATION CODE      Adjuvant emulsion [Int Conf AIDS 1992 Jul
                          19-24;8(2):(abstract no. PoA 2226)]
 CLASSIFICATION CODE      Immunostimulant [Int Conf AIDS 1992 Jul
                          19-24;8(2): abstract no. PoA 2226]
 OTHER MAJOR USES         Vaccine adjuvant [NIAID VEU 005]
 ADVERSE EFFECTS          Adverse effects include mild to moderate
                          local pain at the site of injection, mild
                          erythema at the site of injection, fatigue,
                          myalgia, eyelid burning, feverishness,
                          buzzing in the head, limb pain,
                          indisposition, headache, back pain, dysuria,
                          ear pressure. Laboratory evidence may include
                          transient increase in leukocytes (absolute
                          neutrophilia) starting at 4-6 hours post
                          injection, but never rising above the normal
                          range, transient increase in fibrinogen at 48
                          hours, increased sedimentation rate,
                          transient drop in serum iron at 24 hours.
                          [Int Conf AIDS 1992 Jul 19-24;8(1): (abstract
                          no. MoB 0025] [NIAID VEU 005]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A muramyl tripeptide (MTP)
                          linked covalently with dipalmitoyl
                          phosphatidylethanolamine (PE) [Int Conf AIDS
                          1992 Jul 19-24;8(1):(abstract no. MoB 0025)]
                          [NIAID VEU 005]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: The active ingredient is a
                          fully synthetic lipophilic derivative of the
                          naturally occurring muramyl dipeptide (MDP)
                          [NIAID VEU 005] [Int Conf AIDS 1992 Jul
                          19-24;8(1): abstract no. MoB 0025]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Used as an adjuvant
                          emulsion, MTP-PE/MF59 [NIAID VEU 005] [Int
                          Conf AIDS 1992 Jul 19-24;8(1): abstract no.
                          MoB 0025]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Prepared by emulsion
                          process titled MF59 [NIAID VEU 005] [Int Conf
                          AIDS 1992 Jul 19-24;8(1): abstract no. MoB
                          0025]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: The emulsifier system
                          consists of polysorbate 80 (Tween 80,
                          polyoxyethylene sorbitan monooleate) and
                          sorbitan triolate (Span 85, Arlacel 85)
                          [NIAID VEU 005] [Int Conf AIDS 1995 Jul
                          19-24;8(1): abstract no. MoB 0025]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: The emulsifier system
                          prevents coalescence of the dispersed
                          droplets [NIAID VEU 005] [Int Conf AIDS 1992
                          Jul 19-24;8(1): abstract no. MoB 0025]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Emulsification, by high
                          pressure homogenization, results in a
                          physically stable emulsion with a mean
                          droplet size of less than 200 nm [NIAID VEU
                          005] [Int Conf AIDS 1992 Jul 19-24;8(1):
                          abstract no. MoB 0025]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: In this oil-in-water
                          emulsion, squalene constitutes the oil phase
                          [NIAID VEU 005] [Int Conf AIDS 1992 Jul
                          19-24;8(1): abstract no. MoB 0025]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: MTP-PE is expected to be
                          situated at the interface of the aqueous and
                          oil phases and act as a weak co-emulsifier
                          [NIAID VEU 005] [Int Conf AIDS 1992 July
                          19-24;8(1): abstract no. MoB 0025]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C59H108N6O19PNa x XH20
                          (where X=1-5) [NIAID VEU 005]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 1260 (anhydrous) [NIAID VEU
                          005]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: Amphophilic; forms micellar
                          solutions in water [NIAID VEU 005]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Used  in an oil-water emulsion.
                          [NIAID VEU 005]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intramuscular injection
                          (IM). [Int Conf AIDS 1992 Jul
                          19-24;8(2):(abstract no. PoA 2226)]
 SUBSTANCE DELIVERY DATA  STORAGE: Refrigerate. [NIAID VEU 005]
 MANUFACTURERS            BIOCINE
 REFERENCES               Langenberg AG, Burke RL, Adair SF, Sekulovich
                          R, Tigges M, Dekker CL, Corey L. A
                          recombinant glycoprotein vaccine for herpes
                          simplex type 2: safety and efficacy. Ann
                          Intern Med. 1995 Jun 15;122(12):889-98.
 REFERENCES               Kahn JO, Sinangil F, Baenziger J, Murcar N,
                          Wynne D, Coleman RL, Steimer KS, Dekker CL,
                          Chernoff D. Clinical and immunologic
                          responses to human immunodeficiency virus
                          (HIV) type 1SF2 gp120 subunit vaccine
                          combined with MF59 adjuvant with or without
                          muramyl tripeptide dipalmitoyl
                          phosphatidylethanolamine in non-HIV-infected
                          human volunteers. J Infect Dis. 1994
                          Nov;170(5):1288-91.
 REFERENCES               Valensi JP, Carlson JR, Van Nest GA. Systemic
                          cytokine profiles in BALB/c mice immunized
                          with trivalent influenza vaccine containing
                          MF59 oil emulsion and other advanced
                          adjuvants. J Immunol. 1994 Nov
                          1;153(9):4029-39.
 REFERENCES               Corey H, McElrath H, Keefer M, Paxton W,
                          Sposto R, Chernoff D. A phase I HIV-1 vaccine
                          trial in asymptomatic HIV-infected
                          individuals using Env 2-3 in MF-59 with or
                          without MTP-PE. Int Conf AIDS. 1993 Jun
                                  6-11;9(1):494 (abstract no.
                          PO-B28-2152).
 REFERENCES               Keefer M, Graham B, McElrath J, Matthews T,
                          Chernoff D, Dolin R. Phase I trial of an
                          HIV-1 vaccine candidate, Env 2-3, in
                          combination with MTP-PE/MF59. Int Conf AIDS.
                          1993 Jun 6-11;9(1):252 (abstract no.
                          PO-A29-0708).
 REFERENCES               Keitel W, Couch R, Bond, Adair S, Van Nest G,
                          Dekker C. Pilot evaluation of influenza virus
                          vaccine (IVV) combined with adjuvant.
                          Vaccine. 1993;11(9):909-13.
 REFERENCES               Kahn JO, Birx DL. Vaccines directed against
                          HIV: preventive and therapeutic strategies.
                          AIDS Clin Rev. 1993-94:213-38.
 REFERENCES               Dolin R, Corey L, Graham B, Wright P,
                          McElrath J, Keefer M, Matthews T, Stablein D,
                          Dekker C. Safety and immunogenicity of an HIV
                          vaccine candidate, env 2-3, in combination
                          with MTP-PE/MF59. Int Conf AIDS. 1992 Jul
                          19-24;8(2):A40 (abstract no. PoA 2226).
 REFERENCES               Van Nest G, Barchfeld G, Haigwood N, Ott G,
                          Wentworth P, Steimer K. Novel muramyl
                          tripeptide (MTP-PE) adjuvant formulations for
                          enhancement of immunity to recombinant HIV-1
                          gp120 envelope antigens. Int Conf AIDS. 1990
                          Jun 20-23;6(2):326 (abstract no. 1050).
 ENTRY MONTH              9103
 LAST REVISION DATE       951213
 

SOURCE: National Library of Medicine, Bethesda, MD.  Distributed by AEGIS.
