title: Lack of effect of paracetamol on the pharmacokinetics and metabolism of codeine in man.
abstract: Plasma and urine concentrations of codeine and its measurable metabolites were determined by HPLC in six healthy subjects after a single 30 mg oral dose of codeine either alone or after 7 doses of 1 g paracetamol 8 hourly. After codeine alone, the t1/2 (h), AUC (mumol.l-1.h) and CLR (ml.min-1) for codeine were 2.2, 0.81, and 252 respectively. These were not significantly altered by paracetamol: 2.2, 0.84, and 291 respectively. For codeine-6-glucuronide the values were 2.4, 22.0, and 29.7 respectively. These were not significantly different from those after codeine plus paracetamol: 2.4, 21.9, and 39.6. There were no significant differences between the two treatments in the apparent partial clearances (ml.min-1) of codeine to morphine (88 codeine alone, 70 codeine plus paracetamol), to norcodeine (71 codeine alone, 88 codeine plus paracetamol), and to codeine-6-glucuronide (820 codeine alone, 1022 codeine plus paracetamol). The urinary excretion of codeine-6-glucuronide, morphine, norcodeine, and codeine were not significantly different between the two treatments.
authors.affiliation: Department of Clinical Pharmacology, Royal Adelaide Hospital, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Somogyi
authors.forename: F
authors.initials: F
authors.lastname: Bochner
authors.forename: Z R
authors.initials: ZR
authors.lastname: Chen
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D003061:Codeine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D009020:Morphine / Q000378:metabolism; D013997:Time Factors
chemical_list: C010414:norcodeine; D000082:Acetaminophen; D009020:Morphine; C061773:codeine-6-glucuronide; D003061:Codeine