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

Abstract

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)

The Effect of Low‐Dose Cimetidine (200 mg Twice Daily) on the Pharmacokinetics of Theophylline

“…To evaluate circadian differences, the area under the theophylline serum concentration versus time curve during each dosing interval, AUC (0-12) and AUC (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) , was calculated. In addition, oral clearance was evaluated as CLo (0-12) and CLo (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) . Differences in the pharmacokinetics of theophylline between the day (0-12) and night (12-24) dosing intervals were described descriptively.…”

“…Dietary changes may actually affect theophylline to the same extent as standard doses of cimetidine. 16 Theophylline adverse effects were most common following initiation of treatment. Most of the subjects in this study reported nervousness, tremor, palpitations, mental disturbances, and nausea in the first 2 to 3 days of treatment.…”

“…Formulation variability, several environmental factors, and dietary factors can also affect theophylline oral clearance. [16][17][18][19] Consequently, the intrasubject variability in theophylline pharmacokinetics and variability in the cimetidinetheophylline interaction are important to consider in assessing the drug interaction.…”

The emerging role of pharmacogenetics: implications for clinical psychiatry

“…CYP3A4 enzyme induction has been observed with concomitant use of St. John's wort ( Hypericum perforatum ) which can result in increased metabolism of CYP3A4 substrates [10]. Similarly, food substances found in charbroiled beef, cruciferous vegetables (cabbage and sprouts), high protein diet [43] and constituents of tobacco [44] can induce CYP1A2. On the other hand, inhibition of CYP enzymes may also occur with concurrent use of grapefruit juice containing narigenin [45] that inhibits CYP3A4 which is responsible for metabolism of a large number of psychotropics.…”

The Emerging Role of Pharmacogenetics: Implications for Clinical Psychiatry

“…Dietary factors, herbal medication, chemicals and even pollutants are exogenous agents that may alter the activity of drug-metabolizing enzymes, particularly CYP1A2 and CYP3A4 [41]. Similarly, food substances found in charbroiled beef, cruciferous vegetables (cabbage and sprouts), high protein diet [43] and constituents of tobacco [44] can induce CYP1A2. Studies have shown that Asians and Africans exposed to Western diets and environment do not exhibit the same sensitivity to psychotropics as those living in their native countries [42].…”