OPIOID PHARMACODYNAMICS IN NEONATAL DOGS - DIFFERENCES BETWEEN MORPHINE AND FENTANYL

Clinical experience and laboratory studies suggest that neonates are m ore sensitive than adults to the ventilatory depressant effects of mor phine. Similar sensitivity has been cited, but not demonstrated, for f entanyl. To examine this issue, we determined ventilatory pharmacodyna mics of morphine and fentanyl in 28 dogs aged 2-35 days. During isohyp ercapnia, morphine or fentanyl was infused to depress minute ventilati on by >50% and arterial plasma opioid concentrations were measured. Fo r each drug, an effect compartment pharmacodynamic model was fit to th e values for minute ventilation to determine the steady-state opioid p lasma concentration depressing ventilation by 50% (C-50) and the rate constant for equilibration between plasma concentration and effect (k( eo)). For morphine, there was a marked age-related increase in C-50 bu t no change in k(eo). For fentanyl, there was a small maturational inc rease in C-50 and no change in k(eo). We conclude that there are marke d maturational changes in the ventilatory depressant effects of morphi ne resulting from maturational changes in sensitivity rather than in e quilibration. Maturational changes in the ventilatory effects of fenta nyl are much smaller in magnitude than those for morphine.