Pharmacokinetics of zidovudine and acetaminophen in a patient on chronic acetaminophen therapy
DM Burger,
PL Meenhorst,
CH Koks,
and
JH Beijnen
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.
