Effect of gestational age on morphine half-life (t½), clearance (Cl) and volume of distribution (Vd) is not very clear.On 8 published studies sample size were small.Using published individual infant data we recalculated various pharmacokinetic parameters.Morphine dosage ranged from 0.05-0.15 mg/kg as a single dose or bolus of 10-200 μg/kg followed by 10-30 μg/kg/min as infusion.Data from 140 infants from 8 studies were divided in to 5 subgroups. Gr 1: 26 wks (n=15), Gr 2: 27-30 wks (n=44), Gr 3:31-34 wks (n=35), Gr 4: 35-37 (n=8), Gr 5:>37 wks (n=37).Data were analyzed by regression analysis and t-test. *p <0.05 when compared to Gr1.

Results:(table, M±SD)βt½ was significantly lower and Cl was higher in Gr 5 when compared to Gr 1 (p<.05) The t½ decreased with increasing gest.age(r2=0.32, 0.83 hr/wk gestation, p<.0001). Vd did not change between Gr1 to Gr5. Figure shows mean βt½, Cl and 95% confidence bands. Conclusion: 1) t½ decreased with increasing gest.especially beyond 35 wks.2) Changes in t½ was accompanied by increase in Cl (figure). 3) Vd did not show any changes with gest. 4) intermittent dosing can be given every 8 hr for infants <34 wks and every 4 hr for infants >35wks gest.

Table 1
Full size table
figure 1

Figure 1