Evaluation of the in vivo effect of naproxen on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus.
OBJECTIVE
To determine if therapeutic doses of naproxen affect the in vivo disposition of zidovudine.


METHODS
This was designed as a randomized, two-period, two-treatment, crossover study. The patients were 12 men infected with human immunodeficiency virus who had acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. On two separate occasions 14 days apart, patients received either zidovudine alone (200 mg every 4 hours while awake) or zidovudine (200 mg every 4 hours while awake) and naproxen (500 mg every 12 hours for 4 days). On the morning of the fifth day, each patient received the final dose of each regimen and blood and urine were serially collected for 8 hours. Pharmacokinetic parameters (area under the serum concentration-time curve [AUC], maximum plasma concentration, terminal half-life, renal clearance, and urinary recovery) were assessed for zidovudine and its glucuronide metabolite.


RESULTS
Naproxen had no significant effect (< 10% difference between treatment means, p > 0.15, ANOVA) on the above pharmacokinetic parameters for both zidovudine and its metabolite. Although the power of the study to detect these small differences was < 80% at the 5% significance level, differences ranging from 12.6% for AUC to 38.8% for urinary recovery could be detected with 80% power.


CONCLUSIONS
Therapeutic doses of naproxen do not significantly affect the pharmacokinetic disposition of zidovudine.
Sahai
J
J
Department of Medicine, Ottawa General Hospital, Ontario, Canada.
Gallicano
K
K
Garber
G
G
Pakuts
A
A
Hawley-Foss
N
N
Huang
L
L
McGilveray
I
I
Cameron
D W
DW
D000328:Adult; D000704:Analysis of Variance; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000494:pharmacology*; D011863:Radioimmunoassay; D015215:Zidovudine / Q000493:pharmacokinetics* / Q000627:therapeutic use
D015215:Zidovudine; D009288:Naproxen