Development of N-demethylase activity measured with the 13C-aminopyrine breath test

Jäger‐Roman, Elke; Rating, D.; Platzek, Thomas; Helge, H

doi:10.1007/bf00441496

Cited by 25 publications

(12 citation statements)

References 18 publications

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“…The maximum percentage dose I3CO2 eliminated per hour was lower than that found in the present study. Our results, however, are not directly comparable to those of Jaeger-Roman et al (7) because the C02 production rate was not measured in their study. ' In two of the infants who underwent sequential studies, the increases in drug elimination were quite marked (patients 2 and 16).…”

Section: -contrasting

confidence: 99%

“…Jaeger-Roman et al (7) studied a small number of infants with the aminopyrine breath test and found that the amount of labeled C02 eliminated in breath increased with age. The maximum percentage dose I3CO2 eliminated per hour was lower than that found in the present study.…”

Section: -mentioning

confidence: 99%

“…Although the aminopyrine breath test has been used for a number of years in adults, there is little experience with the application of the test in infants and children (7). Because demethylation is dependent on cytochrome activity, the utilization of the aminopyrine breath test in children affords a unique method to examine the time course of the postnatal development of demethylase function.…”

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confidence: 99%

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Effect of Infant Age on Aminopyrine Breath Test Results

et al. 1985

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Vol. 19, No. 5, 1985 Printed in U.S.A. quantitate I3CO2 elimination of breath, demethylation of aminopyrine was found to be positively correlated to age. By 20 wk of age, some infants had rates of elimination similar to those measured in adults. Absorption was excluded as a limiting variable, because no improvement in oxidation rates was found when the aminopyrine was readministered as an intravenous bolus. Changes in nutritional status and route of feeding (enteral versus parenteral) did not prevent the effect of maturation on aminopyrine elimination. Conclusions: 1) maturational differences are seen in the metabolism of aminopyrine; 2) these differences may reflect immaturity of N-demethylase activity or diversion of the liberated formaldehyde into biosynthetic rather than oxidative pathways. (Pediatr Res 19: 441-445, 1985) 442 SHULMAN ET AL. Effect of Infant Age on Aminopyrine Breath Test Results

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Section: -contrasting

confidence: 99%

Section: -mentioning

confidence: 99%

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Effect of Infant Age on Aminopyrine Breath Test Results

et al. 1985

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“…Using the aminopyrine breath test that monitors the phenobarbital-inducible isoenzymes of P450, age-related changes in aminopyrine demethylase activity have been demonstrated in rats (25), in 1-to 38-wk-old infants (26) and in older children (27). The maturation of activity measured in vitro correlates with drug elimination in vivo (25).…”

Section: Discussionmentioning

confidence: 99%

Maturation of Caffeine N-Demethylation in Infancy: A Study Using the 13CO2 Breath Test

et al. 1988

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ABSTRACT. Four premature neonates and eight infants 1-19 months old received caffeine for apnea. The usual morning oral dose was substituted by 1,3,7 I3C-trimethylxanthine (13C-tri CAF) as the citrate salt. Five breath samples were collected the day before (day 1) and the day of 13C-tri CAF administration (day 2). Plasma (after each breath collection) and urine were collected on day 2. 13C-C02 exhalation was determined by isotope ratio mass spectrometry. Caffeine and its metabolites were measured using high-pressure liquid chromatography. Assessment of the labeled C 0 2 in the breath revealed no detectable I3C-tri CAF N-demethylation activity in infants before 45 wk postconceptional age. However, demethylation (as urinary metabolites) has been detected before that age. Two-, 4-, and 6-h cumulative excretion of 13C-tri CAF as 13C-C02 increased with postnatal age and correlated with caffeine plasma clearance (r = 0.840, p c 0.01). These results were consistent with those obtained for urinary metabolites. In one infant (19 months old) the cumulative excretion of I3C-C02 while crying was 65% of the value observed during quiet breathing. The measurement of caffeine demethylation using the caffeine C 0 2 breath test is feasible in infants and is a safe and noninvasive method to determine age related changes in P450I-dependent N-demethylase activity. (Pediatr Res 23: 632-636, 1988)

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“…It may be as sumed that with such breath analysis mainly specific hepatic functions are assessed in vivo, but it is difficult to prove the quantita tive aspect of this assumption. Nevertheless, breath tests have been employed as apparent indicators of liver function both in animals [4][5][6] and in man [7] with several substrates, aminopyrine being the most thoroughly in vestigated compound for assessment of the cytochrome-P45o-dependent metabolic ca pacity [8][9][10]. With this substrate, the devel opment of the apparent monooxygenase ac tivity during the perinatal period has also been assessed in mice [11].…”

Section: Introductionmentioning

confidence: 99%

CO(2) Breath Tests Using 14C-Caffeine, 14C-Methacetin and 14C-Phenacetin for Assessing Postnatal Development of Monooxygenase Activities in Rats and Marmosets

Krüger¹,

Helge²,

Neubert³

1991

Dev Pharmacol Ther

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The time course in which the activities of cytochrome P(450)-dependent drugmetabolizing enzymes develop during the perinatal period differs for various types of monooxygenases as well as for various animal species. Using [3-methyl^14C]-, [7-methyl^14C]-caffeine, [14CH(3)]-methacetin and [14C(2)H(5)]-phenacetin as substrates in breath tests, the developmental changes in the rates of 14CO(2) formation, due to changes in the activity of monooxygenases, were studied in rats and marmoset monkeys (Callithrix jacchus). In rats a rate of 0.006% of the dose administered/min was found to be exhaled as 14CO(2) in the caffeine breath tests on the 1st day of life. This value increased gradually reaching adult rates of 14CO(2) exhalation after 21 days for [3-methyl^14C]-caffeine and after 25 days for [7-methyl^14C]-caffeine. In marmosets the rate of 14CO(2) exhalation for [3-methyl^14C]- and [7-methyl^14C]- caffeine was also low at birth and developed gradually reaching adult values of 14CO(2) exhalation within 120-200 days. In rats the capacity for dealkylation of methacetin and phenacetin developed much faster compared with caffeine: 9 days postnatally, the exhalation of 14CO(2) reached adult values. Offspring of marmosets reached adult values of 14C02 exhalation at 8 days postnatally when using [14CO(2)]-methacetin as substrate and at 30 days postnatally using [14C(2)H(5)]-phenacetin in the breath test. The results suggest that the monooxygenases for the N-demethylation of caffeine, the O-demethylation of methacetin and the O-deethylation are rather substrate specific in the two species studied. The breath tests used are sensitive methods for assessing the development of different monooxygenases in vivo in rats and marmosets, and they may well (using 13C-labelled substrates) be applicable for studies in children to monitor effects of certain environmental pollutants.

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Development of N-demethylase activity measured with the 13C-aminopyrine breath test

Cited by 25 publications

References 18 publications

Effect of Infant Age on Aminopyrine Breath Test Results

Effect of Infant Age on Aminopyrine Breath Test Results

Maturation of Caffeine N-Demethylation in Infancy: A Study Using the 13CO2 Breath Test

CO(2) Breath Tests Using 14C-Caffeine, 14C-Methacetin and 14C-Phenacetin for Assessing Postnatal Development of Monooxygenase Activities in Rats and Marmosets

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