Pharmacokinetics and Metabolism of [³H] Thebaine

Abstract

1. A method is described for determination of [³H]thebaine in biological materials with sensitivity of 10–20 ng.

2. Following a 5 mg/kg subcutaneous dose of [³H]thebaine to rats, max. brain and plasma concns. were 937 ng/g and 1076 ng/ml at 0.5 and 1 h, respectively; these declined to non-detectable levels at 24 h. The corresponding half-lives of thebaine in rat plasma and brain were 1.1 and 1.5 h, respectively.

3. Free thebaine excreted in 96 h urine and faeces following a 5 mg/kg subcutaneous dose was 16.7 and 4.3% and total radioactivity was 43.4 and 8.4%, respectively.

4. Extensive metabolism of thebaine occured in rat; several metabolites were identified by chromatography, and metabolites were also shown to be present in the brain.

5. Rat plasma proteins and human albumin bound thebaine (1–100 µg/ml) to the extent of 66.7 and 27.3%, respectively; binding to plasma proteins was independent of thebaine concentration.

6. Rapid metabolism and elimination of thebaine prevents its persistance in brain. These findings are discussed in relation to the absence of physical dependence on this drug.