      Document 0107
 DOCN  DRG0107
 UNIQUE IDENTIFIER        DRG-0140
 NAME OF SUBSTANCE        WR 6026 [AmFAR Tx Dir 1993;6(4)]
 REGISTRY NUMBER          57695-04-2
 RELATED REGISTRY NUMBER  5330-29-0 (hydrochloride)
 STANDARD CHEMICAL NAME   8-((6-(diethylamino)hexyl)amino)-6-methoxy-4-
                          methylquinoline [MeSH]
 SYNONYMS                 WR-6026 [MeSH]
 PROTOCOL ID NUMBERS      NIAID ACTG 173
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   WR 6026 has been proven effective against PCP
                          in mice.  Studies on dogs characterize WR
                          6026 as a drug of relatively high systemic
                          clearance, large volume of distribution,
                          relatively short half-life, and low systemic
                          availability, probably due to presystematic
                          elimination in the liver. In recent human
                          trials, WR has been well tolerated in most
                          subjects given doses from 30 mg/day to 120
                          mg/day. [Int Conf AIDS 1993 Jun
                          6-11;9(1):(abstract no PO-B29-2180)] [AmFAR
                          Tx Dir 1993;6(4)] [Eur J Drug Metab
                          Pharmacokinetic 1991; Spec No 3]
 DISEASES STUDIED/TREATED Being investigated as prophylaxis or
                          treatment of PCP in HIV-infected patients
                          [AmFAR Tx Dir 1993;6(4)]
 CLASSIFICATION CODE      Antiprotozoal [AmFAR Tx Dir 1993;6(4)]
 OTHER MAJOR USES         Leishmaniasis [AmFAR Tx Dir 1993;6(4)] [Clin
                          Infect Dis 1994 Dec;19(6)]
 ADVERSE EFFECTS          Only moderate toxicities have been
                          observed, and dose limiting toxicity has
                          not prevented dose-escalation. Two subjects
                          in a blinded study developed a skin rash. GI
                          distress, headache and methemoglobinemia were
                          reported in patients receiving 0.25-1.0
                          mg/kg/day. [Int Conf AIDS Jun
                          6-11;9(1):(abstract no. PO-B29-2180)] [Clin
                          Infect Dis 1994 Dec;19(6)]
 CHEMICAL/PHYSICAL DATA   DRUG DESCRIPTION: One of several
                          8-aminoquinolone analogues developed by the
                          Walter Reed Army Institute for Research
                          [AmFAR Tx Dir 1993;6(4)]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C21H33N3O [CHEMLINE]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 15 and 30 mg gelatin capsules.
                          [NIAID ACTG 173]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [NIAID ACTG 173]
 MANUFACTURERS            University of Iowa
 REFERENCES               Sherwood JA, Gachihi GS, Muigai RK, Skillman
                          DR, Mugo M, Rashid JR, Wasunna KM, Were JB,
                          Kasili SK, Mbugua JM, et al. Phase 2 efficacy
                          trial of an oral 8-aminoquinoline (WR6026)
                          for treatment of visceral leishmaniasis. Clin
                          Infect Dis; VOL 19, ISS 6, 1994, P1034-9.
 REFERENCES               Petty B, Black J, Hendrix C, Bassiakos Y, et
                          al. Escalating multiple-dose safety and
                          tolerance of WR 6026 in HIV-infected
                          subjects. Int Conf AIDS 1993 Jun
                          6-11;9(1):498 (abstract no. PO-B29-2180).
 REFERENCES               Goheen MP, Bartlett MS, Shaw MM, Queener SF,
                          Smith JW. Effects of 8-aminoquinolines on the
                          ultrastructural morphology of Pneumocystis
                          carinii. Int J Exp Pathol 1993
                          Aug;74(4):379-87.
 REFERENCES               Queener SF, Dean RA, Bartlett MS, Milhous WK,
                          Berman JD, Ellis WY, Smith JW. Efficacy of
                          intermittent dosage of 8-aminoquinolines for
                          therapy or prophylaxis of Pneumocystis
                          pneumonia in rats. J Infect Dis 1992
                          Apr;165(4):764-8.
 REFERENCES               Taylor T, Hawkins DR, Morris GR, Chung H.
                          Pharmacokinetics of the anti-leishmanian
                          agent WR 6026 in dogs. Eur J Drug Metab
                          Pharmacokinet 1991;Spec No 3:136-9.
 REFERENCES               Steinhaus RK, Baskin SI, Clark JH, Kirby SD.
                          Formation of methemoglobin and metmyoglobin
                          using 8-aminoquinoline derivatives or sodium
                          nitrite and subsequent reaction with cyanide.
                          J Appl Toxicology 1990 Oct;10(5):345-51.
 ENTRY MONTH              9204
 LAST REVISION DATE       960403
 

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