Two assays for dihydrocodeine in plasma and in urine and their use to determine the bioavailability of a controlled-release product.
A GC method (20 ng/mL quantitation limit) and an HPLC method (37.5 ng/mL quantitation limit) for the analysis of dihydrocodeine in plasma and an HPLC method for dihydrocodeine in urine (2 micrograms/mL quantitation limit) are described. These methods have been used to compare the bioavailability in four subjects of a controlled-release formulation of dihydrocodeine bitartrate (equivalent to 90 mg of base) with that of a solution (equivalent to 3 x 30 mg of base). With each preparation, the mean urinary recovery of dihydrocodeine was approximately 30 mg, and both had a comparable bioavailability. A further study with 12 subjects, each taking the equivalent of 30 mg of base at 12 hourly intervals for 4 d, indicated that the controlled-release formulation produced effective steady-state concentrations of drug whether administered before or after meals, with no accumulation being observed.
Cowan
D A
DA
Drug Control Centre, King's College London, UK.
Woffendin
G
G
Noormohammadi
A
A
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D003061:Codeine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D006801:Humans; D008297:Male
D003692:Delayed-Action Preparations; C014481:dihydrocodeine; D003061:Codeine