Caffeine and theophylline metabolism in newborn and adult human hepatocytes; comparison with adult rat hepatocytes

Liver cell models in in vitro toxicology.

“…It is appropriate to test at least two concentrations, with the highest close to the maximum nontoxic concentration. However, for some drugs, in vitro biotransformation is low and does not reflect the in vivo situation whatever culture conditions are used (204). Such striking quantitative differences are sometimes minimized when metabolites are expressed per cell, as shown by Berthou et al (204) for caffeine.…”

“…However, for some drugs, in vitro biotransformation is low and does not reflect the in vivo situation whatever culture conditions are used (204). Such striking quantitative differences are sometimes minimized when metabolites are expressed per cell, as shown by Berthou et al (204) for caffeine. In addition, the metabolic profile obtained with hepatocytes can be quite different from a metabolic profile obtained from a given compartment in vivo (e.g., urine or plasma) and it misses metabolism in nonhepatic tissues in vivo.…”

Intake of caffeine and other methylxanthines during pregnancy and risk for adverse effects in pregnant women and their foetuses

“…Our knowledge about the enzymology of caffeine metabolism in man (Table 40) has increased during recent years (Kalow, 1985;Berthou et al, 1988Berthou et al, , 1991Butler et al, 1989;Fuh et al, 1992;Tassaneeyakul et al, 1994;Chung and Cha, 1997). CYP1A2 is the most essential enzyme in the metabolism of caffeine, although other CYP enzymes, flavin monooxygenase, and N-acetyltransferase are also involved in its metabolism (Kalow, 1985;Butler et al, 1989;Berthou et al, 1991;Fuh et al, 1992;Tassaneeyakul et al, 1994;Chung and Cha, 1997).…”

“…Clinical documentation for CYP1A2's gradual emergence in the early months of postnatal life is widely available because theophylline and caffeine are extensively used for the treatment of apnea in premature deliveries, newborns, and infants. In premature infants, caffeine is only metabolised to theophylline and is to a large extent excreted unchanged in the urine (Berthou et al, 1988). When CYP1A2 develops after the third to fifth month of life (Sonnier and Cresteil, 1998), N-3 and N-7 demethylations begin, and the infant demonstrates the metabolic pattern that characterises mature hepatic metabolism (Berthou et al, 1988;Kraus et al, 1993;Cazeneuve et al, 1994).…”

“…In premature infants, caffeine is only metabolised to theophylline and is to a large extent excreted unchanged in the urine (Berthou et al, 1988). When CYP1A2 develops after the third to fifth month of life (Sonnier and Cresteil, 1998), N-3 and N-7 demethylations begin, and the infant demonstrates the metabolic pattern that characterises mature hepatic metabolism (Berthou et al, 1988;Kraus et al, 1993;Cazeneuve et al, 1994). Hydroxylation capability matures as early as one month in some children, and may be higher in infants than in adults.…”