      Document 0092
 DOCN  DRG0092
 UNIQUE IDENTIFIER        DRG-0155
 NAME OF SUBSTANCE        Daunorubicin (liposomal) [AmFAR Tx Dir
                          1995;7(4)]
 REGISTRY NUMBER          20830-81-3
 STANDARD CHEMICAL NAME   Free drug daunorubicin:
                          (8S-cis)-8-Acetyl-10-[(3-amino-2,3,6-trideoxy-
                          -alpha-
                          L-lyxo-hexopyranosyl)oxyl-7,8,9,10-tetrahydro-
                          -6,8,11
                          -trihydroxy-1-methoxy-5,12-naphthacenedione
                          [Merck Index 1989]
 SYNONYMS                 Daunoxome [FDA 121A]
 SYNONYMS                 DaunoXome [AmFAR Tx Dir 1995;7(4)]
 SYNONYMS                 VS-103 [Int Conf AIDS 1993 Jun
                          6-11;9(1):(abstract no. WS-B15-3)]
 PROTOCOL ID NUMBERS      FDA 121A
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Liposomal encapsulation may
                          increase the cellular uptake of daunorubicin
                          and reduce systemic toxicities. Daunorubicin
                          hydrochloride used in chemotherapy inhibits
                          the synthesis of nucleic acids; its effect on
                          deoxyribonucleic is particularly rapid and
                          marked. The drug has antimitotic and
                          cytotoxic activity although the precise mode
                          of action is unknown. A mean terminal
                          half-life of 2.8 to 5.2 h for 10 to 80 mg/m2
                          doses was reported. Mean total body clearance
                          ranged from 15.7 to 6.6 ml/min, which is
                          considerably less than free daunorubicin at
                          233 ml/min. The area under the plasma
                          concentration curve was dose dependent and
                          ranged from 16.9 to 378.3 mcg/h/ml. Low
                          levels of daunorubicinol and one aglycone
                          metabolite were detected in plasma at higher
                          doses. [AmFAR Tx Dir 1995;7(4)] [PDR 1995] [J
                          Clin Oncol 1995 Apr;13(4)]
 DISEASES STUDIED/TREATED FDA approved 4/8/96 as first-line therapy for
                          advanced HIV-associated Kaposi's sarcoma
                          [NeXstar Pharmaceuticals Press Release
                          4/30/96]
 CLASSIFICATION CODE      Antineoplastic [USAN 1996]
 OTHER MAJOR USES         Chemotherapy drug (daunorubicin
                          hydrochloride) [PDR 1995]
 ADVERSE EFFECTS          Myelosuppression is the most commonly
                          experienced adverse effect. Vomiting,
                          stomatitis, and alopecia were rare and mild.
                          In AIDS patients with advanced Kaposi's
                          sarcoma severe neutropenia occurred in 2%,
                          while the most common nonhematological
                          toxicities were mild to moderate fatigue, low
                          grade fever and diarrhea. Toxicity was most
                          often related to dosages of 50-60 mg/m2.
                          [Lancet 1993 May 15;341(8855)] [J Clin Oncol
                          1995 Apr;13(4)]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: An intravenous formulation
                          of daunorubicin that has been encapsulated in
                          targeted liposomes [AmFAR Tx Dir 1993;6(4)]
                          [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: Daunorubicin is a cytotoxic
                          anthracycline aminoglycoside antibiotic
                          isolated from Streptomyces coeruleorubidus
                          [PDR 1995] [AmFar Tx Dir 1993;6(4)]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: The free drug
                          daunorubicin is in the form of thin red
                          needle shaped crystals [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORM.: C27H29NO10 (Daunorubicin)
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 527.51 (Daunorubicin)
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 208-209 C (Daunorubicin)
                          [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMP.: C61.47%, H5.54%, N2.66%,
                          O30.33% (Daunorubicin) [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in water, methanol, and
                          aqueous alcohols (Daunorubicin) [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   PHYS. COMMENT: Color of aqueous solution
                          changes from pink in acid pH to blue in
                          alkaline pH [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Intravenous. [AmFAR Tx Dir
                          1995;7(4)] [J Clin Oncol 1995 Apr;13(4)]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Free drug daunorubicin
                          equivalent of 40 mg/m2. [Int Conf AIDS 1992
                          Jul 19-24;8(2):(abstract no. PoB 3123)]
 MANUFACTURERS            Vestar Inc
 REFERENCES               Gill PS, Wernz J, Scadden DT, Cohen P,
                          vonRoenn J, Chew T, Kempin S, Silverberg I,
                          Gonzales G, Rarick MU et al. A randomized
                          trial of liposomal daunorubicin (DX) vs
                          Adriamycin, bleomycin and vincristine (ABV)
                          in 232 patients with advanced AIDS-related
                          Kaposi's sarcoma (Meeting abstract). Proc Ann
                          Meet Am Assoc Cancer Res; 14:A830 1995.
 REFERENCES               Gill PS, Espina BM, Muggia F, Cabriales S,
                          Tulpule A, Esplin JA, Liebman HA, Forssen E,
                          Ross ME, Levine AM. Phase I/II clinical and
                          pharmacokinetic evaluation of liposomal
                          daunorubicin. J Clin Oncol. 1995
                          Apr;13(4):996-1003.
 REFERENCES               Schurmann D, Dormann A, Grunewald T, Ruf B.
                          Successful treatment of AIDS-related
                          pulmonary Kaposi's sarcoma with liposomal
                          daunorubicin. Eur Respir J. 1994
                          Apr;7(4):824-5.
 REFERENCES               Chew T, Jacobs M, Huckabee M, Ross M. A phase
                          II clinical trial of DaunoXome (VS103,
                          liposomal daunorubicin) in Kaposi's sarcoma
                          of AIDS patients. Int Conf AIDS. 1993 Jun
                          6-11;9(1):58 (abstract no. WS-B15-3).
 REFERENCES               Money-Kyrle JF, Bates F, Ready J, Gazzard BG,
                          Phillips RH, Boag FC. Liposomal daunorubicin
                          in advanced Kaposi's sarcoma: a phase II
                          study. Clin Oncol (R Coll Radiol).
                          1993;5(6):367-71.
 REFERENCES               Presant CA, Scolaro M, Kennedy P, Blayney DW,
                          Flanagan B, Lisak J, Presant J. Liposomal
                          daunorubicin treatment of HIV-associated
                          Kaposi's sarcoma. Lancet. 1993 May
                          15;341(8855):1242-3.
 REFERENCES               Ross M, Gill PS, Espina BM, Crossley R,
                          Muggia F, Levine AM. Liposomal daunorubicin
                          (DaunoXome) in the treatment of advanced
                          AIDS-related Kaposi's sarcoma: results of a
                          phase II study. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B107 (abstract no. PoB 3123).
 REFERENCES               Dupont B, Pialoux G, Gonzalez G, Feuillie V.
                          Phase II study of liposomal daunorubicin
                          (DaunoXome) in AIDS related Kaposi's sarcoma.
                          Int Conf AIDS. 1992 Jul 19-24;8(2):B106
                          (abstract no. PoB 3119).
 REFERENCES               Chew T, Jacobs M, Street H, Crossley R. A
                          phase II clinical trial of VS103 (liposomal
                          daunorubicin) in Kaposi's sarcoma in AIDS
                          patients. Int Conf AIDS. 1992 Jul
                          19-24;8(2):B106 (abstract no. PoB 3106).
 REFERENCES               Dormann A, Gruenewald T, Ross ME, Pohle HD,
                          Ruf B, Schueler W. Liposomal-encapsulated
                          cytotoxic agent daunorubicin (LD) versus
                          conventional three-drug chemotherapy (CC) in
                          AIDS patients with Kaposi's sarcoma
                          (KS)--preliminary results. Int Conf AIDS.
                          1992 Jul 19-24;8(1):Th74 (abstract no. ThD
                          1545).
 ENTRY MONTH              9212
 LAST REVISION DATE       960612
 

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