ALTERATIONS IN THEOPHYLLINE METABOLISM DURING THE 1ST YEAR OF LIFE

被引:48
作者
KRAUS, DM
FISCHER, JH
REITZ, SJ
KECSKES, SA
YEH, TF
MCCULLOCH, KM
TUNG, EC
CWIK, MJ
机构
[1] UNIV ILLINOIS,COLL PHARM,DEPT PHARM PRACTICE MC886,833 S WOOD ST,ROOM 276,CHICAGO,IL 60612
[2] UNIV ILLINOIS,DEPT PEDIAT,CHICAGO,IL 60680
[3] COOK CTY HOSP,CHICAGO,IL 60612
关键词
D O I
10.1038/clpt.1993.160
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 mug/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.
引用
收藏
页码:351 / 359
页数:9
相关论文
共 31 条
[1]   MATURATION OF CAFFEINE ELIMINATION IN INFANCY [J].
ARANDA, JV ;
COLLINGE, JM ;
ZINMAN, R ;
WATTERS, G .
ARCHIVES OF DISEASE IN CHILDHOOD, 1979, 54 (12) :946-949
[2]   PHARMACOKINETIC ASPECTS OF THEOPHYLLINE IN PREMATURE NEWBORNS [J].
ARANDA, JV ;
SITAR, DS ;
PARSONS, WD ;
LOUGHNAN, PM ;
NEIMS, AH .
NEW ENGLAND JOURNAL OF MEDICINE, 1976, 295 (08) :413-416
[3]   ONTOGENY OF HUMAN CAFFEINE AND THEOPHYLLINE METABOLISM [J].
ARANDA, JV ;
SCALAIS, E ;
PAPAGEORGIOU, A ;
BEHARRY, K .
DEVELOPMENTAL PHARMACOLOGY AND THERAPEUTICS, 1984, 7 :18-25
[4]   CAFFEINE AND THEOPHYLLINE METABOLISM IN NEWBORN AND ADULT HUMAN HEPATOCYTES - COMPARISON WITH ADULT-RAT HEPATOCYTES [J].
BERTHOU, F ;
RATANASAVANH, D ;
ALIX, D ;
CARLHANT, D ;
RICHE, C ;
GUILLOUZO, A .
BIOCHEMICAL PHARMACOLOGY, 1988, 37 (19) :3691-3700
[5]   THEOPHYLLINE METABOLISM DURING THE 1ST MONTH OF LIFE AND DEVELOPMENT [J].
BONATI, M ;
LATINI, R ;
MARRA, G ;
ASSAEL, BM ;
PARINI, R .
PEDIATRIC RESEARCH, 1981, 15 (04) :304-308
[6]   METABOLISM OF THEOPHYLLINE TO CAFFEINE IN PREMATURE NEWBORN-INFANTS [J].
BORY, C ;
BALTASSAT, P ;
PORTHAULT, M ;
BETHENOD, M ;
FREDERICH, A ;
ARANDA, JV .
JOURNAL OF PEDIATRICS, 1979, 94 (06) :988-993
[7]   PLASMA XANTHINE LEVELS IN LOW-BIRTH-WEIGHT INFANTS TREATED OR NOT TREATED WITH THEOPHYLLINE [J].
BRAZIER, JL ;
RENAUD, H ;
RIBON, B ;
SALLE, BL .
ARCHIVES OF DISEASE IN CHILDHOOD, 1979, 54 (03) :194-199
[8]   MATURATIONAL CHANGES OF THEOPHYLLINE PHARMACOKINETICS IN PRETERM INFANTS [J].
DOTHEY, CI ;
TSERNG, KY ;
KAW, S ;
KING, KC .
CLINICAL PHARMACOLOGY & THERAPEUTICS, 1989, 45 (05) :461-468
[9]   CLINICAL ASSESSMENT OF GESTATIONAL AGE IN NEWBORN INFANT [J].
DUBOWITZ, LM ;
DUBOWITZ, V ;
GOLDBERG, C .
JOURNAL OF PEDIATRICS, 1970, 77 (01) :1-+
[10]   THEOPHYLLINE PHARMACOKINETICS IN PREMATURE-INFANTS WITH APNEA [J].
GIACOIA, G ;
JUSKO, WJ ;
MENKE, J ;
KOUP, JR .
JOURNAL OF PEDIATRICS, 1976, 89 (05) :829-832