Document 0534
 DOCN  M9440534
 TI    Atovaquone: a review.
 DT    9404
 AU    Haile LG; Flaherty JF; Division of Clinical Pharmacy, School of
       Pharmacy, University of; California, San Francisco 94143.
 SO    Ann Pharmacother. 1993 Dec;27(12):1488-94. Unique Identifier : AIDSLINE
       MED/94138137
 AB    OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics,
       clinical efficacy, and safety of atovaquone. DATA IDENTIFICATION: An
       English-language literature search using MEDLINE (1984-1993), programs
       and abstracts of the 30th, 31st, and 32nd Interscience Conferences on
       Antimicrobial Agents and Chemotherapy, program and abstracts of the VIII
       International Conference on AIDS, and unpublished information from
       Burroughs Wellcome, the manufacturer of atovaquone. STUDY SELECTION: All
       available pharmacokinetic and clinical trials were reviewed. DATA
       EXTRACTION: Study quality was assessed by a critical appraisal of study
       design and methods. Pharmacokinetic studies were evaluated for sampling,
       methods used to determine pharmacokinetic properties, and the presence
       of concentration-response and concentration-toxicity relationships.
       Clinical trials were assessed primarily for comparative efficacy and
       toxicity. RESULTS: Atovaquone is a novel hydroxynaphthoquinone with
       potent activity against Pneumocystis carinii and Toxoplasma gondii. Its
       pharmacokinetic properties are characterized by relatively poor
       bioavailability, excretion almost exclusively through the feces, lack of
       hepatic metabolism and urinary excretion, low steady-state plasma
       concentrations, high protein binding, and a long elimination half-life
       (50-70 h). Results from comparative clinical trials in AIDS patients
       with mild-to-moderate P. carinii pneumonia (PCP) reveal similar overall
       treatment success rates for atovaquone, trimethoprim/sulfamethoxazole
       (TMP/SMX), and pentamidine. Treatment failure because of lack of
       therapeutic response was significantly greater in patients who received
       atovaquone compared with those treated with TMP/SMX (p = 0.002). More
       atovaquone-patients experienced treatment failure compared with their
       pentamidine-treated counterparts, although statistical significance was
       not achieved. Treatment failure secondary to drug toxicity was
       significantly higher in the TMP/SMX- and pentamidine-treated patients (p
       < or = 0.01). Atovaquone has not been studied for PCP prophylaxis.
       Limited data exist on the use of atovaquone for toxoplasmic encephalitis
       (TE); however, results from an open trial reveal that the drug may be
       useful in treating this disorder. To date, atovaquone has been well
       tolerated by most patients administered the drug. The most common
       adverse effects include maculopapular rash, gastrointestinal
       disturbances, and fever. Atovaquone is considerably more costly than
       other oral agents used to treat PCP. CONCLUSIONS: Atovaquone appears to
       be better tolerated but less effective than TMP/SMX and pentamidine in
       the treatment of mild-to-moderate PCP. There is not enough information
       available on the use of atovaquone for PCP prophylaxis or the treatment
       of TE to definitively describe its efficacy. Comparative clinical trials
       are needed to assess its role in this clinical setting.
 DE    Animal  Antifungal Agents/CHEMISTRY/PHARMACOKINETICS/*THERAPEUTIC USE
       Antiprotozoal Agents/CHEMISTRY/PHARMACOKINETICS/*THERAPEUTIC USE
       AIDS-Related Opportunistic Infections/DRUG THERAPY  Clinical Trials
       Human  Male  Naphthoquinones/CHEMISTRY/PHARMACOKINETICS/*THERAPEUTIC USE
       Pneumonia, Pneumocystis carinii/DRUG THERAPY  Toxoplasmosis,
       Cerebral/DRUG THERAPY  JOURNAL ARTICLE  REVIEW  REVIEW, TUTORIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).