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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Islam
Samira I
SI
Drug Monitoring Unit, King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia. dmukauh@yahoo.com
Ali
Ahmed S
AS
Sheikh
Amal A
AA
Fida
Nadia M
NM
D000628:Aminophylline / Q000627:therapeutic use; D001049:Apnea / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy*; D008297:Male; D013806:Theophylline / Q000493:pharmacokinetics*
D001993:Bronchodilator Agents; D000628:Aminophylline; D013806:Theophylline