TY - JOUR
T1 - Alterations in theophylline metabolism during the first year of life
AU - Kraus, Donna M.
AU - Fischer, James H.
AU - Reitz, Shirley J.
AU - Kecskes, Susan A.
AU - Yeh, Tsu F.
AU - McCulloch, Kristine M.
AU - Tung, Elizabeth C.
AU - Cwik, Michael J.
PY - 1993/1/1
Y1 - 1993/1/1
N2 - Maturational changes in theophylline disposition were evaluated in 52 infants (gestational age, 24 to 40 weeks; postnatal age, 2 to 69 weeks) receiving maintenance theophylline therapy. Theophylline and metabolites were measured in serum and urine at steady state, and the influence of clinical parameters on the maturational changes was analyzed by multiple stepwise linear regression. Theophylline clearance and urine metabolite pattern reached adult values at 55 weeks' postconceptional age. Serum caffeine concentrations greater than 1 µg/ml occurred in infants up to 50 weeks' postconceptional age. Disappearance of serum caffeine concentrations and maturation of theophylline clearance were primarily related (p < 0.001) to development of the demethylation pathway to 3‐methylxanthine. Postconceptional age was the major factor (p < 0.001) explaining the interpatient variability in theophylline clearance (r2 = 0.57), serum caffeine to theophylline ratio (r2 = 0.46), and urinary excretion of theophylline (r2 = 0.51), caffeine (r2 = 0.49), 1,3‐methyluric acid (r2 = 0.32), 1‐methyluric acid (r2 = 0.53), and 3‐methylxanthine (r2 = 0.58). Our findings indicate that postconceptional age rather than postnatal age should be used as a maturational marker during theophylline therapy in infancy. Clinical Pharmacology and Therapeutics (1993) 54, 351–359; doi:
AB - Maturational changes in theophylline disposition were evaluated in 52 infants (gestational age, 24 to 40 weeks; postnatal age, 2 to 69 weeks) receiving maintenance theophylline therapy. Theophylline and metabolites were measured in serum and urine at steady state, and the influence of clinical parameters on the maturational changes was analyzed by multiple stepwise linear regression. Theophylline clearance and urine metabolite pattern reached adult values at 55 weeks' postconceptional age. Serum caffeine concentrations greater than 1 µg/ml occurred in infants up to 50 weeks' postconceptional age. Disappearance of serum caffeine concentrations and maturation of theophylline clearance were primarily related (p < 0.001) to development of the demethylation pathway to 3‐methylxanthine. Postconceptional age was the major factor (p < 0.001) explaining the interpatient variability in theophylline clearance (r2 = 0.57), serum caffeine to theophylline ratio (r2 = 0.46), and urinary excretion of theophylline (r2 = 0.51), caffeine (r2 = 0.49), 1,3‐methyluric acid (r2 = 0.32), 1‐methyluric acid (r2 = 0.53), and 3‐methylxanthine (r2 = 0.58). Our findings indicate that postconceptional age rather than postnatal age should be used as a maturational marker during theophylline therapy in infancy. Clinical Pharmacology and Therapeutics (1993) 54, 351–359; doi:
UR - http://www.scopus.com/inward/record.url?scp=0027490183&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027490183&partnerID=8YFLogxK
U2 - 10.1038/clpt.1993.160
DO - 10.1038/clpt.1993.160
M3 - Article
C2 - 8222476
AN - SCOPUS:0027490183
SN - 0009-9236
VL - 54
SP - 351
EP - 359
JO - Clinical Pharmacology & Therapeutics
JF - Clinical Pharmacology & Therapeutics
IS - 4
ER -