Pharmacokinetics of theophylline in preterm neonates during the first month of life

ABSTRACT

The present work aimed to estimate the theophylline pharmacokinetic parameters [TH-PKP] in preterm neonates with apnea during the first month of life in order to optimize its dosage regimen. Fifty preterm neonates enrolled in the study with recurrent apnea were admitted during 1998-2000 to the Neonatal Intensive Care Unit of Maternity and Children's Hospital, Al-Mosaida, Jeddah, Kingdom of Saudi Arabia. Criteria for this study were preterm with gestational age [GA] of 26-33 weeks [mean +/- SD 30 +/- 3.9]. They received TH of 3-6 mg/kg loading dose [LD] followed by maintenance dose [MD] of 0.5 - 3.0 mg/kg/12 hours. Eight of these patients received phenobarbital and 19 received cimetidine concomitantly for at least 7 days. Blood samples were taken one hour post LD and at steady state [Css]. Theophylline levels were determined by fluorescence polarization immunoassay. Phenobarbital significantly enhanced TH clearance [CL] and reduced its half-life [t0.5] but cimetidine had no significant effect. Excluding patients receiving phenobarbital. The mean +/- SD TH-PKP were volume of distribution [Vd] = 0.77 +/- 0.25 L/kg; elimination rate constant [Ke] = 0.027 +/- 0.011 h-1; CL = 0.019 +/- 0.006 L/h/kg, t0.5 = 30.7 +/- 12.1. There was marked intra patient variability in all TH-PKP. In view of the results and practical considerations, initial dosage regimen to attain a TH Css level within the therapeutic range [6-12 ug/ml] was suggested LD 6-7 mg/kg, MD 1.5 - 2.0 mg/kg/12 hours. To compensate for maturation changes or drug interaction, a method, based on estimation of individual TH CL, was described for adjusting MD