12 PHARMACOKINETICS AKD PULMONARY FUNCTION FOLLOWING A TEST DOSE OF I.V. SALBUTAMCL IN VENTILATED INFANTS KITH BROKCHOPULMOBARY DYSPLASIA (EPD)

Pharmacokinetics and pharmacodynamics of i.v. salbutamol (1.0 μg/kg/min for 30 min) were studied in 6 ventilator-dependent infants with BPD (GA 24-28 weeks, postnatal age 50-90 days). Passive respiratory system compliance (Crs), resistance (R), heart rate (HR), blood pressure (EP) and arterial blood gas tensions (ABG) were recorded before and up to 6 hours post-infusion. Elimination T1/2 of salbutamol was 133±27 min X ± SEM), distribution volume (Vd) 1277±486 ml/kg and clearance 7.72±3.33 ml/kg/min. T1/2 appears to be shorter than in healthy adults, probably due to smaller Vd associated with tissue hypoperfusion. Crs improved immediately in 5 patients. Increments ranged from 0.45-2.04 ml/cm H2O/m body length (23-145% of pre-drug values). The subsequent fall of Crs paralleled the fall of drug levels. The 6th infant had a delayed rise in Crs at 6 hrs post-infusion. This may be explained by a particularly small volume of distribution (200 ml/kg), suggesting delayed delivery of tlie drug to tissue receptors. R fell in 4 infants (22-35% of pre-drug levels). HR rose from X=153/min to X=206/min, concurrent with peak drug levels. No consistent changes were seen for BP and ABG. We conclude that following this test dose of i.v. salbutamol in infants with BPD, (1) T1/2=133±27 min; (2) Crs improves immediately in most patients; (3) increased Crs is not always accompanied by decreased R; (4) increased Crs is not associated with improved AEG; (5) tachycardia is a serious side-effect.