Pharmacokinetics of Morphine and its Surrogates IX: Discrepancies among Infused Buprenorphine Plasma Concentrations Sampled From Different Veins

Abstract

When blood was drawn from the brachial vein of the dog upon infusion of buprenorphine hydrochloride in saline through a plastic catheter into the jugular vein, the post-infusion jugular vein plasma concentrations observed during the first 15 min of the post-infusion distributive phase were significantly higher than the highest observed brachial vein plasma concentrations at the time of cessation of infusion. When blood was drawn from the jugular vein following infusion of buprenorphine hydrochloride into the left brachial vein, the post-infusion left brachial plasma concentrations during the first 15 min of the post-infusion distributive phase were significantly higher than the highest jugular and contralateral brachial vein concentrations observed just before and after the cessation of infusion. Dependent on whether the plasma concentrations sampled from the infused catheter or another catheter were used, the apparent calculated total body clearances differed by 25–39%. These results demonstrated that the observed differences in the post-infusion buprenorphine concentrations in plasma obtained from different veins were not due to any drug-induced changes in the circulatory physiology of the dog. Evidence is presented to show that the discrepancies were due to the repartitioning of the catheter-bound drug into the blood drawn through the catheter for assay, which significantly increased the apparent blood concentration of drug, not-withstanding the fact that only an extremely small fraction (0.004–0.009) of a simulated 1–3-h infused dose partitioned into the plastic catheter. When buprenorphine hydrochloride was administered by a bolus injection, there was no significant partitioning of drug into the infusion catheter. When buprenorphine glucuronide solution was infused through the jugular catheter, post-infusion plasma concentrations from both the jugular and brachial veins were the same, indicating no significant binding of the glucuronide to the plastic catheter. In general, caution must be exercised in interpreting pharmacokinetic data obtained from plasma samples that were drawn through the same plastic catheter as was used in the prolonged infusion of lipophilic drugs.