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Heroin Addiction and Related Clinical Problems: 2012, 14, 1 (pages: 45 - 58)

A compartmental model for the pharmacokinetics of heroin and its metabolites in man.

Urso R., Montefrancesco G., Rigato M.

Summary: A compartmental model was used to describe the pharmacokinetics of heroin, 6-monoacetylmorphine, morphine and glucuronides. The parameters of the model were estimated by pooling the observations collected and published in various studies, and were used to predict the effect of a reduced rate of glucuronidation and renal excretion on the plasma profile of morphine and its glucuronides after single and multiple administrations of morphine. Simulations were performed by assuming that some rate constants were representative of the rates of morphine glucuronidation and renal excretion. The results showed that renal impairment may produce more extensive drug accumulation during multiple dose treatments than an impaired morphine metabolism (leading to as much as a tenfold increase in the plasma levels of morphine after a 90% reduction of renal clearance). This happens because enterohepatic recycling takes place fast enough to allow morphine to stay in equilibrium with its glucuronides in blood, while the pool of morphine and morphine-glucuronides is only slowly cleared by the kidneys.