Premium
Codeine Disposition in Sickle Cell Patients Compared With Healthy Volunteers
Author(s) -
Mohammed Sumia S.,
Ayass Mohab,
Mehta Paulette,
Kedar Amos,
Gross Samuel,
Derendorf Hartmut
Publication year - 1993
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1993.tb01956.x
Subject(s) - pharmacokinetics , codeine , cmax , volume of distribution , chemistry , pharmacology , in vivo , oral administration , half life , medicine , morphine , microbiology and biotechnology , biology
The pharmacokinetics of codeine were determined after oral administration of codeine sulfate (60 mg) with sickle cell patients (SCPs) and healthy controls (HCs). Plasma concentrations of codeine were measured by reversed‐phase high‐pressure liquid chromatography with fluorescence detection. Pharmacokinetic parameters were calculated using both compartmental and noncompartmental analysis. No significant differences were observed in time to reach maximum peak plasma concentration (tmax) (1.0 ± 0.4 versus 1.4 ± 1.0 hours), maximum peak plasma concentration (Cmax) (172 ± 25 versus 225 ± 97 ng/mL), area under the curve (AUC∞) (590 ± 96 versus 779 ± 234 ng*h/mL), and Cl/F (104 ± 17 versus 89 ± 27 L/h) between SCPs and HCs. Conversely, significant 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 observed 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 relatively high‐extraction drug that is primarily eliminated by metabolism in the liver. Generally, the clearance of such drugs is approximately equal to hepatic blood flow and is not affected by changes in protein binding. Therefore, the change in t1/2 observed in SCPs can be attributed to changes in volume of distribution rather than clearance.