Back to Search
Start Over
Codeine disposition in sickle cell patients compared with healthy volunteers
- Source :
- Journal of clinical pharmacology. 33(9)
- Publication Year :
- 1993
-
Abstract
- 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 infinity) (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.
- Subjects :
- Pharmacology
Volume of distribution
Adult
medicine.medical_specialty
Dose-Response Relationship, Drug
Chemistry
Codeine
Area under the curve
Cmax
Anemia, Sickle Cell
Endocrinology
Pharmacokinetics
Oral administration
In vivo
Anesthesia
Internal medicine
Blood plasma
medicine
Humans
Pharmacology (medical)
medicine.drug
Half-Life
Subjects
Details
- ISSN :
- 00912700
- Volume :
- 33
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Journal of clinical pharmacology
- Accession number :
- edsair.doi.dedup.....96af9daf6f34dec11dbe9a5083feb93e