      Document 0052
 DOCN  DRG0052
 UNIQUE IDENTIFIER        DRG-0195
 NAME OF SUBSTANCE        Cycloserine [USAN 1996]
 REGISTRY NUMBER          68-41-7
 STANDARD CHEMICAL NAME   3-Isoxazolidinone,4-amino [USAN 1996]
 SYNONYMS                 Orientomycin [Merck Index 1989]
 SYNONYMS                 PA-94 [Merck Index 1989]
 SYNONYMS                 106-7 [Merck Index 1989]
 SYNONYMS                 Closina [Merck Index 1989]
 SYNONYMS                 Farmiserina [Merck Index 1989]
 SYNONYMS                 Micoserina [Merck Index 1989]
 SYNONYMS                 Oxamycin [Merck Index 1989]
 SYNONYMS                 Seromycin [USAN 1996]
 PROTOCOL ID NUMBERS      NIAID ACTG 238
 SECONDARY SOURCE ID      DRG
 PHARMACOLOGICAL ACTION   MODE OF ACTION: Inhibits cell-wall synthesis
                          in susceptible strains of gram-positive and
                          gram-negative bacteria and in Mycobacterium
                          tuberculosis. After oral administration,
                          cycloserine is readily absorbed from the
                          gastrointestinal tract, with peak blood
                          levels occurring in 4 to 8 hours. Blood
                          levels of 25 to 30 mg/ml can generally be
                          maintained with the usual dosage of 250 mg
                          twice a day, although the relationship of
                          plasma levels to dosage is not always
                          consistent. Concentrations in the
                          cerebrospinal fluid, pleural fluid, fetal
                          blood, and mother's milk approach those found
                          in the serum. Detectable amounts are found in
                          ascitic fluid, bile, sputum, amniotic fluid,
                          and lung and lymph tissues. Approximately 65%
                          of a single dose of cycloserine can be
                          recovered in the urine within 72 hours after
                          oral administration. The remaining 35% is
                          apparently metabolized to unknown substances.
                          The maximum excretion rate occurs 2 to 6
                          hours after administration, with 50% of the
                          drug eliminated in 12 hours. [PDR 1995]
 DISEASES STUDIED/TREATED Used against tuberculosis after failure of
                          adequeate treatment with the primary
                          antituberculosis drug [Drug Evaluations
                          Annual 1992] [AHFS Drug Information 1995]
 DISEASES STUDIED/TREATED Should be administered with other effective
                          agents [Drug Evaluations Annual 1992] [AHFS
                          Drug Information 1995]
 CLASSIFICATION CODE      Antibacterial [USAN 1996]
 OTHER MAJOR USES         Pulmonary and extrapulmonary tuberculosis and
                          acute urinary tract infections [PDR 1995]
 SUBSTANCE INTERACTIONS   Interacts with alcohol or with concurrently
                          administered ethionamide or isoniazid. [PDR
                          1995]
 ADVERSE EFFECTS          Adverse effects include convulsions,
                          drowsiness and somnolence, headache, tremor,
                          dysarthria, vertigo,confusion and
                          disorientation with loss of memory, psychoses
                          (possibly with suicidal tendencies),
                          character changes, hyperirritability,
                          aggression, paresis, hyperreflexia,
                          paresthesia, seizures, coma, allergy, skin
                          rash, and sudden development of congestive
                          heart failure (in patients receiving 1 to 1.5
                          grams). [PDR 1995]
 CONTRAINDICATIONS        Contraindicated in patients with seizure
                          disorders, depression, severe anxiety or
                          psychosis, renal insufficiency, excessive use
                          of alcohol, and hypersensitivity. [PDR 1995]
 CHEMICAL/PHYSICAL DATA   DESCRIPTION: A broad-spectrum antibiotic that
                          is produced by a strain of Streptomyces
                          orchidaceus and has also been synthesized
                          [PDR 1995]
 CHEMICAL/PHYSICAL DATA   MOLECULAR FORMULA: C3H6N2O2 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   MOLECULAR WEIGHT: 102.09 [USAN 1996]
 CHEMICAL/PHYSICAL DATA   STABILITY: Forms salts with acids and bases.
                          Neutral or acid solutions are unstable [Merck
                          Index 1989]
 CHEMICAL/PHYSICAL DATA   STABILITY: Aqueous solutions buffered to pH
                          10 with sodium carbonate can be stored
                          without loss of potency for one week at
                          refrigerator temperatures [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   SOLUBILITY: Soluble in water and alkaline
                          solutions [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL DESCRIPTION: White to off-white
                          powder [PDR 1995]
 CHEMICAL/PHYSICAL DATA   PHYSICAL COMMENT: Aqueous solutions have a pH
                          around 6 [Merck Index 1989]
 CHEMICAL/PHYSICAL DATA   ELEMENTAL COMPOSITION: C35.29%, H5.92%,
                          N27.44%, O31.34% [Merck Index 1989]
 SUBSTANCE DELIVERY DATA  DOSAGE FORM: 250 mg capsules. [PDR 1995]
 SUBSTANCE DELIVERY DATA  MODE OF DELIVERY: Oral. [PDR 1995]
 SUBSTANCE DELIVERY DATA  STORAGE: Store at controlled room
                          temperature, 15 to 30 C. [PDR 1995]
 MANUFACTURERS            Eli Lilly and Company
 REFERENCES               Katz MH. Effect of HIV treatment on
                          cognition, behavior, and emotion. Psychiatr
                          Clin North Am. 1994 Mar;17(1):227-30.
 REFERENCES               Heifets LB. Antimycobacterial drugs. Semin
                          Respir Infect. 1994 Jun;9(2):84-103.
 REFERENCES               Yew WW, Wong CF, Wong PC, Lee J, Chau CH.
                          Adverse neurological reactions in patients
                          with multidrug-resistant pulmonary
                          tuberculosis after coadministration of
                          cycloserine and ofloxacin [letter]. Clin
                          Infect Dis. 1993 Aug;17(2):288-9.
 REFERENCES               Rastogi N, David HL. Mode of action of
                          antituberculous drugs and mechanisms of drug
                          resistance in Mycobacterium tuberculosis. Res
                          Microbiol. 1993 Feb;144(2):133-43.
 REFERENCES               Peloquin CA. Pharmacology of the
                          antimycobacterial drugs. Med Clin North Am.
                          1993 Nov;77(6):1253-62.
 REFERENCES               Peloquin CA. Dosage of antimycobacterial
                          agents [letter, comment]. Clin Pharm. 1991
                          Sep;10(9):664-5.
 ENTRY MONTH              9403
 LAST REVISION DATE       951213
 

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