Why such a large discrepancy?

My question concerns blood codeine levels. The table found at MLO at this address: www.mlo-online.com/clr/searchdrugs.asp?class=l lists therapeutic blood levels for codeine of 13-33 nanograms per milliliter. The same table gives a toxic blood level for codeine of 1.1 micrograms per milliliter (= 1,100 nanograms per milliliter). I compared this to Winek's table found at the Fisher Scientific site here: http://fscimage.fishersci.com/we-bimages_FSC/downloads/winek.pdf.

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Winek's table lists therapeutic level for codeine of 0.03-0.34 micrograms per milliliter (= 30-340 nanograms per milliliter). Winek's table does not give a toxic range of levels, but does give a lethal level of 1.6 micrograms per milliliter (= 1600 nanograms per milliliter). There is a large discrepancy in the therapeutic range listed in these two sources: MLO's table gives 13-33 and Winek's table gives 30-340 nanograms per milliliter.

The toxic range given in the MLO table of greater than 1,100 would seem to be pretty consistent with the lethal level given in Winek's table of 1,600. I was hoping that perhaps you could look at the very large discrepancy for the therapeutic range between the two tables and that maybe you could help me understand how there could be this large of a difference (one is 13-33 and the other is 30-340).

--Keath Wade, MD

Satilla Regional Medical Laboratory

Waycross, GA

Daniel M. Baer, MD, and Robert H. Williams, MD, respond: The data in the table was taken from: Poisoning and Toxicology Handbook, Third Edition, by Jerrold B. Leikin, Frank P. Paloucek from Lexi-Comp Inc., 2002. It is not surprising that a variety of values are listed in the literature. Codeine is prescribed for several different medical indications, and is given in widely different doses depending on whether it is a cough suppressant and used in a cough syrup, given for mild pain in a compound medication with an analgesic such as acetaminophen (Tylenol) with codeine, or used alone for moderate pain at a higher dose. As a tablet, codeine is given as 15, 30, 60 mg tablets, but there is also a solution that contains 15 mg/5 mL = 3 mg; that would probably give you a peak level of 0.001 ug/mL or 10 ng/mL (right around the lower end of the therapeutic range that we cited). Pharmacokinetic studies show that a 15-mg dose produces a peak level of 0.03 ug/mL or 30 ng/mL. A 60-mg dose gives a peak level Of 0.11 ug/mL or 110 ng/mL.