Summary:The population pharmacokinetics of theophylline were studied in 35 neonates receiving aminophylline suppositories for the treatment of apnoea of prematurity. Routinely measured theophylline serum concentrations (n = 138, range 3ndash;20 mg/L) were modelled in NONMEM according to a one-compartment model. The influence of a number of clinical and demographic factors, e.g., weight (range 0.8ndash;2.5 kg) and postnatal age (2ndash;80 days), on clearance/bioavailability (CL/F) and volume/bioavailability (V/F) was investigated. Both these parameters were found to significantly correlate to weight alone in a directly proportional manner:CL/F= 40 plusmn; 2 ml/h/kg andV/F= 1.3 plusmn; 0.2 L/kg. The absorption was best described by a first-order process, having a half-life of 1.6 plusmn; 0.7 h. The interindividual variability inCL/Fwas 25percnt;, whereas the same estimates inV/Fand in the first-order absorption rate constant could not be obtained. The residual variability in theophylline concentrations was modelled with additive error with an estimated standard deviation of 1.78 mg/L. From these results, it was concluded that rectal administration of aminophylline in neonates is a therapeutically acceptable alternative to oral administration. The convenience gained by rectal, compared to oral, administrations may compensate, in many instances, for the possibly slightly higher variability inCL/Fof the former.
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