Document 0160
 DOCN  M9470160
 TI    Pharmacokinetics of zidovudine and acetaminophen in a patient on chronic
       acetaminophen therapy.
 DT    9409
 AU    Burger DM; Meenhorst PL; Koks CH; Beijnen JH; Department of Pharmacy,
       Slotervaart Hospital, Amsterdam, The; Netherlands.
 SO    Ann Pharmacother. 1994 Mar;28(3):327-30. Unique Identifier : AIDSLINE
       MED/94250987
 AB    OBJECTIVE: To report a case of a potential interaction between
       acetaminophen and zidovudine in a patient who had used high daily doses
       of acetaminophen over many years. CASE SUMMARY: A 43-year-old man
       presented with HIV-1 infection, recurrent oral candidiasis, and chronic
       use of acetaminophen, codeine, and diazepam before he started zidovudine
       therapy. Although literature was available regarding short-term combined
       use of acetaminophen and zidovudine, information was lacking on
       zidovudine therapy and kinetics after long-term use of acetaminophen.
       Acetaminophen and zidovudine pharmacokinetics were determined on several
       occasions. The results showed extremely rapid absorption of both drugs
       (tmax the time to reach maximum concentration, 10-15 minutes for
       acetaminophen and 15-20 minutes for zidovudine) and, consequently,
       relatively high maximum plasma concentration (Cmax). No influence on
       other pharmacokinetic parameters of either drug could be detected.
       Because the effect of high Cmax values of zidovudine is unknown, the
       patient was treated with a third of the dose of zidovudine used at that
       time (zidovudine 100 mg q6h). No toxicity or opportunistic infections
       developed within the next 8 months, after which the patient died of a
       cause unrelated to HIV infection. DISCUSSION: The observed
       pharmacokinetic profiles of both drugs are discussed and compared with
       two studies dealing with zidovudine therapy in combination with
       short-term use of acetaminophen and with a case report of
       acetaminophen-induced hepatotoxicity during concomitant use of
       zidovudine. CONCLUSIONS: Long-term use of acetaminophen may accelerate
       the absorption of zidovudine. Although other causes cannot be ruled out,
       there was no influence on other pharmacokinetic parameters of
       zidovudine. No influence of zidovudine on acetaminophen concentrations
       was found. Combined use of zidovudine 100 mg q6h and acetaminophen 500
       mg q4h appeared to be safe and effective for at least eight months.
 DE    Acetaminophen/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS  Acquired
       Immunodeficiency Syndrome/DRUG THERAPY/*METABOLISM  Administration, Oral
       Adult  Case Report  Comparative Study  Drug Administration Schedule
       Drug Interactions  Homosexuality  Human  *HIV-1  Injections, Intravenous
       Male  Time Factors  Zidovudine/ADMINISTRATION & DOSAGE/*PHARMACOKINETICS
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
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