The steady-state bioavailability of a controlled-release (CR) oxycodon
e tablet was compared with that of an immediate release (IR) oxycodone
solution in a randomized, analytically masked, multiple-dose, crossov
er study in 24 normal subjects. Each subject received either one 10-mg
CR oxycodone tablet every 12 hours for 4 days or 5 mt of a 1-mg/1 mt
IR oxycodone solution every 6 hours for 4 days. Steady state was achie
ved after approximately 1 day of dosing. The mean (+/-SD) maximum plas
ma oxycodone concentrations for CR oxycodone and IR oxycodone were 15.
1 +/- 4.7 ng/mL and 15.6 +/- 4.4 ng/mL, respectively. The time to maxi
mum concentration (T-max) was approximately twice as long for CR oxyco
done (3.2 +/- 2.2 hours) as for IR oxycodone (1.4 +/- 0.7 hours) (P =
0.005). The area under the plasma concentration-time curve from 0 to 1
2 hours at steady state was 103.6 +/- 40.0 ng . h/mL for CR oxycodone
and 99.0 +/- 35.8 ng . h/mL for IR oxycodone. Except for T-max, there
were no significant differences in pharmacokinetic parameters between
treatments. Approximately twice as many adverse experiences, several o
f longer duration than noted with CR oxycodone, were reported with IR
oxycodone. The bioavailability of the CR tablet was equal to that of t
he IR solution; however, the rate of oxycodone absorption from the CR
tablet was slower than that from the TR solution, as shown by the T-ma
x value. The use of CR oxycodone will allow selection of the most clin
ically appropriate nonopioid analgesic, as well as independent titrati
on and dosing, thereby enhancing therapeutic flexibility.