The effect of diet upon serum concentrations of theophylline.

Thompson, PJ; Skypala, Isabel; Dawson, Susan; Mcallister, W. A. C.; Warwick, Margaret

doi:10.1111/j.1365-2125.1983.tb02160.x

Cited by 23 publications

(7 citation statements)

References 11 publications

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“…The data are further evidence that the effects of the dietary protein/carbohydrate ratio on drug metabolism in humans are quite consistent and are manifest under a variety of conditions. Previously, protein intake was shown to affect drug oxidations not only in normal subjects but also in individuals subject to energy restriction (231, malnutrition (241, liver disease (25) or pulmonary disease (26,27). The present results indicate that the dietary proteinicarbohydrate ratio can also influence drug metabolism when cytochrome P-450 enzymes are partially inhibited by cimetidine.…”

Section: Hepatologysupporting

confidence: 47%

Diet and cimetidine induce comparable changes in theophylline metabolism in normal subjects

Anderson

1991

Hepatology

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This study compared the effects of diet and cimetidine on theophylline metabolism and examined interactions between these effects. Twelve men received a high-protein diet for 15 days and at another time a high-carbohydrate diet also for 15 days. Cimetidine, 800 mg daily at bedtime, was administered on days 10 through 15 of each dietary period. Theophylline metabolism was studied after the administration of a single intravenous 3 mg/kg dose on days 8 and 15 of each dietary period. Changing from a high-protein to a high-carbohydrate diet decreased theophylline clearance by about the same extent (30% +/- 10%) as treatment with cimetidine (37% +/- 5% during a high-protein diet and 30% +/- 5% during a high-carbohydrate diet). Cimetidine did not significantly influence the effects of diet on theophylline clearance. Conversely, dietary composition did not influence the degree of inhibition of theophylline metabolism induced by cimetidine. Depending on the direction of the change in protein/carbohydrate ratio, the effects of diet and cimetidine treatment were either additive (theophylline clearance was most prolonged during the high-carbohydrate regimen with concurrent cimetidine administration) or counteractive (increasing the dietary protein/carbohydrate ratio at least partially counteracted the inhibitory effect of cimetidine). In individual subjects, effects of cimetidine on theophylline metabolism were somewhat more consistent than diet-induced changes. The results are further evidence that diet and drugs can have similar effects on hepatic drug metabolism rates in humans. Variations in diet over time and individual differences in responses to diet may provide the potential for considerable instability of drug metabolism rates in free-living subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Hepatologysupporting

confidence: 47%

Diet and cimetidine induce comparable changes in theophylline metabolism in normal subjects

Anderson

1991

Hepatology

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“…To model high dietary theobromine intake (6 mg/kg/day), we chose a 7-day period of daily consumption of dark chocolate. Furthermore, because other dietary constituents such as protein and carbohydrate can alter methylxanthine elimination rates in man, 9,12,18 the diets of our subjects were standardized to avoid effects from such interference.…”

mentioning

confidence: 99%

High levels of methylxanthines in chocolate do not alter theobromine disposition

Shively

Tarka

Arnaud

et al. 1985

Clin Pharmacol Ther

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Theobromine disposition was measured twice in 12 normal men, once after 14 days of abstention from all methylxanthines and once after 1 week of theobromine (6 mg/kg/day) in the form of dark chocolate. Mean theobromine t 1/2, apparent volume of distribution, and clearance after abstinence from all methylxanthines were 10.0 hours, 0.76 L/kg, and 0.88 ml/min/kg. High daily doses of chocolate for 1 week did not change these values. After subjects abstained from methylxanthines, urinary radioactivity over 72 hours after a single, oral dose of [8-14C]theobromine consisted of 42% 7-methylxanthine, 20% 3-methylxanthine, 18% theobromine, 10% 7-methyluric acid, and 10% 6-amino-5[N-methylformylamino]-1-methyluracil. A week of daily theobromine consumption in the form of dark chocolate also did not alter this urinary profile of theobromine and its metabolites. Although these results might appear to differ from other reports of inhibition of theobromine elimination after five consecutive daily doses of theobromine in aqueous suspensions, both the rate and extent of absorption of theobromine in chocolate were less than that of theobromine in solution. Relative bioavailability of theobromine in chocolate was 80% that of theobromine in solution. This reinforces the fundamental principle that both the metabolic and the therapeutic consequences of a particular chemical can differ when that chemical is given in the pure compared with the dietary form.

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“…While the influence of diet on theophylline metabolism is not well documented, recent studies in animals and man have shown that dietary protein levels may have a significant effect on the hepatic metabolism of drugs such as theophylline. As in the case of studies in the elderly population, theophylline metabolism has been reported to be decreased (Jung 1985b;Juan et al 1986) or unchanged (Thompson et al 1983;Eriksson et al 1983) in protein deficiency when compared to a normal protein diet. The decreased clearance of theophylline is consistent with in vitro findings that there is a general reduction in the activity of the microsomes in protein deficient rats (Dickerson et al 1976;Hayes et al 1978) primarily due to a reduction in the specific enzyme activity, which is reflected in the decrease in the cytochrome P-450 content and activity of the liver (Mgbodile et al 1973).…”

Section: Discussionmentioning

confidence: 90%

The Effects of Age and Dietary Protein Restriction on the Pharmacokinetics of Theophylline in the Rat

Jung

Nanavaty

1990

Pharmacology & Toxicology

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The influence of dietary protein levels on theophylline kinetics was examined in male Fischer 344 virgin rats of 2, 14 and 20 months of age fed for four weeks on a 23% (control) or 5% (low) protein diet ad libitum. Protein deficiency led to a significant decrease in body weight gain for the 2 month old rats (10.9% versus 26.5%). In addition, decreases in total body weight of 7.5% and 15.3% were seen for the 14 and 20 month old rats, respectively, on a low protein diet. Total proteins and albumin levels in plasma were not significantly affected by age or dietary protein levels. After intravenous administration of 10 mg/kg aminophylline, the average mean residence time (MRT) was significantly longer in 20 month old rats as compared to the younger rats, while 14 month old rats had a greater elimination rate constant than the 2 and 20 month old rats. There were significant reductions in the mean steady-state apparent volume of distribution (Vss) in the 2 and 14 month old rats on a low protein diet of 31% and 18%, respectively, while there was no difference between the diets in 20 month old rats. In addition, the Vss decreased from 0.71 L/kg to 0.57 L/kg in the 2 and 20 month old rats, respectively, on a normal protein diet. Dietary protein deficiency led to a significant reduction of total body clearance from approximately 73 to 45 ml/hr/kg in the 2 and 14 month old rats.2+p

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The effect of diet upon serum concentrations of theophylline.

Cited by 23 publications

References 11 publications

Diet and cimetidine induce comparable changes in theophylline metabolism in normal subjects

Diet and cimetidine induce comparable changes in theophylline metabolism in normal subjects

High levels of methylxanthines in chocolate do not alter theobromine disposition

The Effects of Age and Dietary Protein Restriction on the Pharmacokinetics of Theophylline in the Rat

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