CODEINE DISPOSITION IN SICKLE-CELL PATIENTS COMPARED WITH HEALTHY-VOLUNTEERS

The pharmacokinetics of codeine were determined after oral administrat ion of codeine sulfate (60 mg) with sickle cell patients (SCPs) and he althy controls (HCs). Plasma concentrations of codeine were measured b y reversed-phase high-pressure liquid chromatography with fluorescence detection. Pharmacokinetic parameters were calculated using both comp artmental and noncompartmental analysis. No significant differences we re observed in time to reach maximum peak plasma concentration (tmax) (1.0 +/- 0.4 versus 1.4 +/- 1.0 hours), maximum peak plasma concentrat ion (Cmax) (172 +/- 25 versus 225 +/- 97 ng/mL), area under the curve (AUCinfinity) (590 +/- 96 versus 779 +/- 234 ngh/mL), and Cl/F (104 /- 17 versus 89 +/- 27 L/h) between SCPs and HCs. Conversely, signific ant differences were observed in mean residence time (MRT) (3.7 +/- 0. 3 versus 4.7 +/- 0.3 hours) and half-life (t1/2) (1.7 +/- 0.2 versus 2 .8 +/- 0.3 hours). In a separate study, significant differences were o bserved in the in vitro plasma protein binding of codeine in SCPs (66. 0 +/- 8.6%) and HCs (30.5 +/- 2.7%) as well as in vivo binding (68.4 /- 11.1% for SCPs versus 29.2 +/- 3.4% for HCs). Codeine is a relative ly high-extraction drug that is primarily eliminated by metabolism in the liver. Generally, the clearance of such drugs is approximately equ al to hepatic blood flow and is not affected by changes in protein bin ding. Therefore, the change in t1/2 observed in SCPs can be attributed to changes in volume of distribution rather than clearance.