      Document 0168
 DOCN  DRG0168
 UNIQUE IDENTIFIER        DRG-0079
 NAME OF SUBSTANCE        Diclazuril [USAN 1996]
 REGISTRY NUMBER          101831-37-2
 RELATED REGISTRY NUMBER  R 64,433
 STANDARD CHEMICAL NAME   Benzeneacetonitrile,
                          2,6-dichloro-2-(4-chlorophenyl)-4-
                          (4,5-dihydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl-
                          ). [USAN 1996]
 SYNONYMS                 Clinacox [USAN 1990]
 SYNONYMS                 (p-Chlorophynyl)(2,6-dichloro-4-(4-5-dihydro--
                          3,5-dioxo-as-triazin-2-(3H)-yl)phenyl)
                          acetonitrile [USAN 1996]
 SYNONYMS                 2,6-dichloro-alpha-(4-chlorophenyl)-4-(4,5-di-
                          hydro-3,5-dioxo-1,2,4-triazin-2(3H)-yl)benzen-
                          eacetonitrile [MeSH]
 SYNONYMS                 DCL [Int Conf AIDS 1991 Jun 16-21;7(2):
                          (abstract no. W.B. 2318)]
 SYNONYMS                 DCZL [Int Conf AIDS 1990 Jun 20-23;6(1):
                          (abstract no. Th.B. 520)]
 PROTOCOL ID NUMBERS      FDA 038A
 PROTOCOL ID NUMBERS      FDA 038B
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Diclazuril completely
                          interrupts the life cycle of coccidial
                          microorganisms. It has potent activity
                          against various stages; oocyst, schizonts,
                          merozuites, micro and macro gametocytes. It
                          is believed that it will interrupt the life
                          cycle of the microorganism at a very early
                          stage. In one study of diclazuril
                          pharmacokinetics 11 patients were tested.
                          Mean peak plasma concentrations of 0.16 mg/1
                          were reached at 12 hours for all but two
                          subjects (DCL peak at 8 hours). The mean
                          terminal half-life was 84.8 hours. Diclazuril
                          was not detected in the CSF samples. This
                          data suggest slow absorption, low peak plasma
                          levels, and a long half-life. Currently
                          research is focusing on letrazuril, an oral
                          fluorine-based congener of diclazuril. In
                          preclinical studies, the drug is more readily
                          absorbed than diclazuril. [AmFAR Tx Dir
                          1993;6(3)] [Int Conf AIDS 1991 Jun
                          16-21;7(2):(abstract no. W.B. 2318] [Lancet
                          1989, Jun 17;1]
 DISEASES STUDIED/TREATED Isospora and cryptosporidium infection in HIV
                          patients [Int Conf AIDS Jun 16-21;7(2):
                          (abstract no. W.B.2318)]
 CLASSIFICATION CODE      Antiprotozoal [Lancet 1989, Jun 17;1]
 OTHER MAJOR USES         Veterinary uses, coccidiostat in poultry
                          [USAN 1996]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: New benzeacetonitrile with
                          anticoccidial activity [Lancet 1989, June
                          17;1]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 407.64 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C17H9CL3N4O2 [USAN 1996]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: Capsules. [FDA 38A]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [Int Conf AIDS Jun
                          16-21;7(2): (abstract no. W.B. 2318)]
 MANUFACTURERS            Janssen
 REFERENCES               Limson-Pobre RN, Merrick S, Gruen D, Soave R.
                          Use of diclazuril for the treatment of
                          isosporiasis in patients with AIDS [letter].
                          Clin Infect Dis. 1995 Jan;20(1):201-2.
 REFERENCES               Moretti MV, Menichetti F, Pauluzzi S.
                          Diclazuril (DCL) pharmacokinetic in patients
                          with HIV infection. Int Conf AIDS. 1991 Jun
                          16-21;7(2):261 (abstract no. W.B. 2318).
 REFERENCES               Foster BC, Wilson DL, Tryphonas H, Whitehouse
                          LW, Khan SR. A pre-clinical in vitro
                          toxicological model using human lymphocytes.
                          Int Conf AIDS. 1991 Jun 16-21;7(1):100
                          (abstract no. M.A.1034).
 REFERENCES               Menichetti F, Moretti MV, Marroni M, Papili
                          R, Di Candilo F. Diclazuril for
                          cryptosporidiosis in AIDS [letter]. Am J Med.
                          1991 Feb;90(2):271-2.
 REFERENCES               Connolly GM, Youle M, Gazzard BG. Diclazuril
                          in the treatment of severe cryptosporidial
                          diarrhoea in AIDS patients [letter]. AIDS.
                          1990 Jul;4(7):700-1.
 REFERENCES               Soave R, Dieterich D, Kotler D, Gassyuk E,
                          Tierney AR, Liebes L, Legendre R. Oral
                          diclazuril therapy for cryptosporidiosis. Int
                          Conf AIDS. 1990 Jun 20-23;6(1):252 (abstract
                          no. Th.B.520).
 REFERENCES               Connolly G, Youle M, Gazzard B. Diclazuril in
                          the treatment of cryptosporidial diarrhoea in
                          AIDS. Int Conf AIDS. 1990 Jun 20-23;6(2):384
                          (abstract no. 2122).
 REFERENCES               Kayembe K, Desmet P, Henry MC, Stoffels P.
                          Diclazuril for Isospora belli infection in
                          AIDS [letter]. Lancet. 1989 Jun
                          17;1(8651):1397-8.
 ENTRY MONTH              9003
 LAST REVISION DATE       951031
 

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