Dihydrocodeine pharmacokinetics

Pharmacokinetic properties Like codeine, dihydrocodeine is metabolized by CYP2D6 yielding the active metabolite dihydromorphine (Ammon et al., 1999). N-Demethylation... 

Ammon, S., Hofmann, U., Griese, E. U., Gugeler, N., Mikus, G. Pharmacokinetics of dihydrocodeine and its active metabolite after single and multiple oral dosing, Br. J. Clin. Pharmacol. 1999, 48, 317-22. 

This chapter concentrates on some drug choices in acute rather than chronic pain, but the same principles can be used to determine the appropriateness of other types of analgesic. The drugs considered in this section are paracetamol, non-steroidal anti-inflammatories (NSAIDs specifically diclofenac, ibuprofen, indometacin, naproxen, sulindac and tenoxicam) and opioids (codeine, dihydrocodeine, morphine, pethidine and tramadol). Unless otherwise stated, all pharmacokinetic data originate from standard reference sources [1-5] and apply to adults only. 

There is a scarcity of information regarding use of codeine, dihydrocodeine and tramadol in patients with liver impairment. On the basis of pharmacokinetic properties, dihydrocodeine may be preferred over codeine. Owing to a lack of information and the potentially detrimental characteristics of tramadol, other opioids should be used in preference if possible. 

The absolute bioavailability of only a few drug compounds is affected by ESKD. An increase in bioavailability as the result of a decrease in metabolism during the drug s firstpass through the gastrointestinal tract and liver has been noted for some /3-blockers (i.e., bufu-ralol, oxprenolol, propranolol, and tolamolol), dextropropoxyphene, and dihydrocodeine. Although the bioavailability of these compounds is increased, clinical consequences (development of excessive or unexpected adverse effects) have only been demonstrated with dextropropoxyphene and dihydrocodeine. The lack of association between the pharmacokinetic profile and clinical consequences of the /3-blockers may result from an alteration in the responsiveness of patients with renal disease to these agents, as has been reported with propranolol in the elderly. ... 

The analgesic effects of codeine, and probably also hydrocodone, are reduced or abolished by quinidine. Quinidine alters the pharmacokinetics of dihydrocodeine and oxycodone, but this does not appear to alter their effects. 

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