      Document 0130
 DOCN  DRG0130
 UNIQUE IDENTIFIER        DRG-0117
 NAME OF SUBSTANCE        Pentoxifylline [USAN 1996]
 REGISTRY NUMBER          6493-05-6
 STANDARD CHEMICAL NAME   3,7-Dihydro-3,7-dimethyl-1-(5-oxohexyl)-1H-pu-
                          rine-2,6-dione [Merck Index 1989]
 SYNONYMS                 Trental [USAN 1996]
 SYNONYMS                 Oxpentifylline [USAN 1996]
 SYNONYMS                 Vazofirin [Merck Index 1989]
 SYNONYMS                 Azupental [Merck Index 1989]
 SYNONYMS                 Durapental [Merck Index 1989]
 SYNONYMS                 Rentylin [Merck Index 1989]
 SYNONYMS                 Torental [Merck Index 1989]
 SYNONYMS                 Xiphen [Merck Index 1989]
 PROTOCOL ID NUMBERS      NIAID ACTG 160
 PROTOCOL ID NUMBERS      FDA 188A
 SECONDARY SOURCE ID      BL 191 [USAN 1996]
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Pentoxifylline reduces the
                          replication of HIV-1 in vitro in acutely
                          infected PBMC and cultured human T-cells.
                          Pentoxifylline indirectly inhibits HIV-1,
                          possibly through inhibition of the NF-kappa B
                          binding protein. Pentoxifylline also inhibits
                          the production of tumor necrosis factor (TNF,
                          cachetin), a naturally occurring cytokine
                          with many functions in the human immune
                          system. Researchers have reported that
                          recombinant TNF upregulates HIV-1 expression
                          in vitro in chronically infected T-cell
                          lines. It has also been shown that TNF
                          antagonizes the anti-HIV effect of AZT in
                          vitro. In HIV infected people, TNF levels are
                          elevated and may be implicated in the
                          progression of the disease as well as the
                          wasting syndrome associated with HIV
                          infection. Pentoxifylline is known to improve
                          the flow properties of the blood by
                          decreasing its viscosity and has recently
                          been found to enhance renal function. [AmFAR
                          Tx Dir 1995;7(4)] [PDR 1995] [Ren Fail
                          1993;15(2)]
 DISEASES STUDIED/TREATED Modulator of tumor necrosis factor and HIV
                          replication [AmFAR Tx Dir 1995;7(4)]
 CLASSIFICATION CODE      Hemorrheologic [AHFS Drug Information 1995]
 CLASSIFICATION CODE      Immunomodulator [AmFAR Tx Dir 1995;7(4)]
 CLASSIFICATION CODE      Antiretroviral [AmFAR Tx Dir 1995;7(4)]
 CLASSIFICATION CODE      Vasodilator [USAN 1996]
 OTHER MAJOR USES         Indicated for the treatment of patients with
                          intermittent claudication on the basis of
                          occlusive arterial disease of the limbs [PDR
                          1995]
 SUBSTANCE INTERACTIONS   May interact with anticoagulants.
                          Pentoxifylline enhances the anti-HIV effect
                          of ddI and AZT. [AmFAR Tx Dir 1995;7(4)] [PDR
                          1995]
 ADVERSE EFFECTS          Adverse effects include fevers, nausea,
                          vomiting, dizziness, bloating, flushing,
                          arrhythmia, angina, diarrhea, headache, and
                          insomnia. [PDR 1995] [AmFAR Tx Dir 1995;7(4)]
 CONTRAINDICATIONS        Contraindicated in patients with previously
                          indicated intolerance to this compound or
                          methylxanthines such as caffeine,
                          theophylline, and theobromine. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A tri-substituted xanthine
                          derivative [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: Bitter tasting,
                          colorless needles from methanol [Merck Index
                          1989]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C13H18N4O3 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 278.31 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MELTING POINT: 105 C [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C56.10%, H6.52%,
                          N20.13%, O17.25% [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in water, benzene,
                          ethanol, sparingly soluble in toluene [Merck
                          Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Pink, film-coated oblong tablets
                          (400 mg). [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at controlled room temperature
                          (59-86 F). Protect from light. [PDR 1995]
 MANUFACTURERS            Hoechst-Roussel
 REFERENCES               Landman D, Sarai A, Sathe SS. Use of
                          pentoxifylline therapy for patients with
                          AIDS-related wasting: pilot study. Clin
                          Infect Dis. 1994 Jan;18(1):97-9.
 REFERENCES               Sonnabend J, Buimovici-Klein E, Freeman K,
                          Smith B, Mohan V, Harrington M.
                          Pentoxifylline (PTX) as a TNF inhibitor in
                          HIV+ individuals. Int Conf AIDS. 1994 Aug
                          7-12;10(2):101 (abstract no. PA0285).
 REFERENCES               Cohen CJ, Dezube BJ, Day JM, Andradas V,
                          Gagnon S, Rieker PP. The impact of
                          pentoxifylline on quality of life. Int Conf
                          AIDS. 1994 Aug 7-12;10(1):213 (abstract no.
                          PB0283).
 REFERENCES               Navarro A, Pizarro A, Herranz P, Aguayo M,
                          Leon M, Pujol E. Treatment of aphthous oral
                          ulcers with pentoxifylline. Int Conf AIDS.
                          1994 Aug 7-12;10(1):183 (abstract no.
                          PB0158).
 REFERENCES               Luke DR, McCreedy BJ, Sarnoski TP, Bookout
                          JB, Johnston AM, Lell JE, Wiggan EB, Bell N,
                          Limjuco RA, Guthrie KI, et al. Phase I/II
                          study of pentoxifylline with zidovudine on
                          HIV-1 growth in AIDS patients. Int J Clin
                          Pharmacol Ther Toxicol. 1993
                          Jul;31(7):343-50.
 REFERENCES               Dezube BJ, Lederman MM, Pardee AB, Chapman B,
                          Korvick J, Crumpacker CS. Pentoxifylline
                          (Trental, PTX) decreases tumor necrosis
                          factor (TNF) & may decrease HIV replication
                          in AIDS patients. Int Conf AIDS. 1993 Jun
                          6-11;9(1):492 (abstract no. PO-B28-2142).
 REFERENCES               Sonnabend JA, Smith B, Buimovici-Klein E,
                          Mohan V. Trental as an anti-TNF agent in HIV
                          infection. Int Conf AIDS. 1993 Jun
                          6-11;9(1):245 (abstract no. PO-A28-0664).
 REFERENCES               Mole L, Margolis D, Holodnly M. A pilot study
                          of pentoxifylline in HIV infected patients
                          with CD4+ lymphocyte counts less than 400
                          cells/mm3. Int Conf AIDS. 1993 Jun
                          6-11;9(1):488 (abstract no. PO-B26-2116).
 REFERENCES               Luke DR, Sarnoski TP, Bell N, Dennis S.
                          Influence of pentoxifylline on renal function
                          in HIV-seropositive patients. Ren Fail.
                          1993;15(2):181-8.
 REFERENCES               Zhang L, Dezube BJ, Ahlers CM, Pardee AB,
                          Crumpacker CS. Pentoxifylline (trental)
                          enhances the antiretroviral activity of
                          didanosine (dideoxyinosine, ddI). Int Conf
                          AIDS. 1992 Jul 19-24;8(2):A57 (abstract no.
                          PoA 2326).
 ENTRY MONTH              9106
 LAST REVISION DATE       951213
 

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