The Journal of pharmacy and pharmacology
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J. Pharm. Pharmacol. · Sep 2001
Pharmacokinetic-pharmacodynamic modelling of human insulin: validity of pharmacological availability as a substitute for extent of bioavailability.
A method for assessing the extent of bioavailability (EBA) of human insulin from pharmacological data was determined. The time course governing increases in the plasma concentration of immuno-reactive insulin (IRI), as well as its pharmacological effects (glucodynamics), was determined after the intravascular administration of varying doses of human insulin. Pharmacokinetic (PK), pharmacodynamic (PD), and link models were constructed to elucidate the quantitative relationship between plasma IRI levels and pharmacological effects. ⋯ The area under the effect-time curves (AUE) obtained following subcutaneous applications of the Osmotic Mini Pump were calculated in a model-independent manner, in addition to pharmacological availabilities (PA), which were estimated against the reference (intravascular) formulations. The estimated PA values varied from 312% to 78%, in accordance with the intravascular input rates of the reference formulations. This indicates that PA should not be used as a substitute for EBA, unless data involving similar intravascular dosing rates to that of the reference formulations is available.