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M9470160.TXT
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1994-07-02
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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
protected by Copyright Law (Title 17, U.S.Code).