      Document 0103
 DOCN  DRG0103
 UNIQUE IDENTIFIER        DRG-0144
 NAME OF SUBSTANCE        Atevirdine mesylate [USAN 1996]
 REGISTRY NUMBER          138540-32-6
 RELATED REGISTRY NUMBER  U-87201E
 STANDARD CHEMICAL NAME   1-[3-(Ethylamino)-2-pyridyl]-4-[(5-methoxyind-
                          ol-2-yl)  carbonyl]-piperazine
                          monomethanesulfon ate [USAN 1996]
 SYNONYMS                 Atevirdine [AmFAR Tx Dir 1993;6(4)]
 SYNONYMS                 ATV [Int Conf AIDS 1993 Jun
                          6-11;9(1):(abstract no. PO-A26-0643)]
 PROTOCOL ID NUMBERS      NIAID ACTG 199
 PROTOCOL ID NUMBERS      FDA 117A
 PROTOCOL ID NUMBERS      FDA 210A
 PROTOCOL ID NUMBERS      NIAID ACTG 187
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: BHAP compounds are
                          non-nucleoside chemicals with anti-HIV
                          activity. BHAP compounds have in vitro
                          activities comparable to other non-nucleoside
                          reverse transcriptase inhibitors
                          (nevirapine). However, all these compounds
                          have unique structures. U-87201E is believed
                          to function as a reverse transcriptase
                          inhibitor.  Resistance to BHAP compounds
                          develops rapidly in vitro. BHAP-resistant
                          virus results from a single amino acid
                          substitution at codon 236. The development of
                          this resistance has been reported to
                          sensitize HIV-1 RT (reverse transcriptase) to
                          inhibition by other non-nucleoside RT
                          inhibitors. Atevirdine (U-87201E) is active
                          against clinical HIV-1 isolates. In a
                          clinical trial of U-87201E and AZT in 20
                          patients with CD4 counts < 500/cubic mm, 5/9
                          patients treated for > 16 weeks had HIV-1
                          isolates sensitive to U-87201E, while 4/9
                          developed resistance to U-87201E between
                          weeks 6 and 24. [AmFAR Tx Dir 1995;7(4)]
                          [AmFar Tx Dir 1993;6(4)] [NIAID ACTG 199]
                          [NIAID ACTG 187]
 DISEASES STUDIED/TREATED Primary HIV infection [AmFAR Tx Dir
                          1995;7(4)]
 CLASSIFICATION CODE      Antiretroviral [AmFAR Tx Dir 1995;7(4)]
 SUBSTANCE INTERACTIONS   BHAP compounds are mutually competitive with
                          nevirapine. [AmFAR Tx Dir 1993;6(4)]
 ADVERSE EFFECTS          Two subjects receiving U-87201E and AZT
                          developed grade III fevers, one subject
                          developed a rash and four subjects developed
                          palpitations. [AmFAR Tx Dir 1995;7(4)]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: A bis(heteroaryl)piperazine
                          (BHAP) compound [AmFAR Tx Dir 1995;7(4)]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [NIAID ACTG 187]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 50 and 200 mg tablets. [NIAID
                          ACTG 187]
 SUBSTANCE DELIVERY DATA  STORAGE: Store between 15 and 30 C (59 and 87
                          F). [NIAID ACTG 187]
 MANUFACTURERS            Upjohn Company
 REFERENCES               Been-Tiktak AM, Vrehen HM, Schneider MM, van
                          der Feltz M, Branger T, Ward P, Cox SR, Harry
                          JD, Borleffs JC. Safety, tolerance, and
                          pharmacokinetics of atevirdine meyslate
                          (U-87201E) in asymptomatic human
                          immunodeficiency virus-infected patients.
                          Antimicrob Agents Chemother. 1995
                          Mar;39(3):602-7.
 REFERENCES               Reichman RC, Morse GD, Demeter LM, Resnick L,
                          Bassiakos Y, Fischl M, Para M, Powderly W,
                          Leedom J, Greisberger C, et al. Phase I study
                          of atevirdine, a nonnucleoside reverse
                          transcriptase inhibitor, in combination with
                          zidovudine for human immunodeficiency virus
                          type 1 infection. ACTG 199 Study Team. J
                          Infect Dis. 1995 Feb;171(2):297-304.
 REFERENCES               Roberts S, Bawdon R, Sobhi S, Dax J, Gilstrap
                          L 3rd, Wimberly D. The maternal-fetal
                          transfer of bisheteroypiperazine (U-87201-E)
                          in the ex vivo human placenta. Am J Obstet
                          Gynecol. 1995 Jan;172(1 Pt 1):88-91.
 REFERENCES               Shelton MJ, Morse GD, Borin MT, Driver MR,
                          Wajszczuk CP, DeRemer MF, Lee K, Fischl MA.
                          Didanosine (ddI) reduces atevirdine (ATV)
                          absorption. Program abstr Intersci Conf
                          Antimicrob Agents Chemother. 1994 Oct
                          4-7;:82.
 REFERENCES               Wagner KF, Mayers DL, Cox SR, Batts DH. A
                          pilot phase I study of oral monotherapy with
                          U-87201E (atevirdine, ATV) in late stage HIV
                          disease. Int Conf AIDS. 1994 Aug
                          7-12;10(2):209 (abstract no. PB0848)
 REFERENCES               Brew BJ, Dunbar N, Druett J. Pilot study of
                          the efficacy of atevirdine in AIDS dementia
                          complex (ADC). Int Conf AIDS. 1994 Aug
                          7-12;10(1):70 (abstract no. 232B).
 REFERENCES               Reichman R, Demeter L, Fischl M, Para M,
                          Powderly W, Leedom J, Resnick L, Morse G,
                          Timpone J, Batts D, et al. Phase I study of
                          atevirdine (ATV), a non-nucleoside reverse
                          transcriptase inhibitor (NNRTI). Natl Conf
                          Hum Retroviruses Relat Infect (1st). 1993 Dec
                          12-16;:159.
 REFERENCES               Morse G, Fischl M, Leedom J, Batts D, Cox S,
                          Reichman R. Atevirdine (ATV) pharmacokinetics
                          (PK) and dosage requirements during a
                          concentration-targeted (CT) phase I study
                          (ACTG 199). Int Conf AIDS 1993 Jun
                          6-11;9(1):477 (abstract no. PO-B26-2050).
 REFERENCES               Demeter LM, Resnick L, Tarpley WG, Fischl M,
                          Para M, Reichman RC. Prolonged sensitivity of
                          HIV-1 isolates to atevirdine (ATV) in a phase
                          I clinical trial of ATV and zidovudine (ZDV)
                          (ACTG 199). Int Conf AIDS 1993 Jun
                          6-11;9(1):242 (abstract no. PO-A26-0643).
 REFERENCES               Vasudevachari MB, Battista C, Lane HC,
                          Psallidopoulos MC, Zhao B, Cook J, Palmer JR,
                          Romero DL, Tarpley WG, Salzman NP. Prevention
                          of the spread of HIV-1 infection with
                          nonnucleoside reverse transcriptase
                          inhibitors. Virology. 1992 Sep;190(1):269-77.
 ENTRY MONTH              9206
 LAST REVISION DATE       960115
 

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