Ten healthy volunteers were fed (1) a control diet for 10 days, (2) the same control diet for 3 additional days and a brussels sprouts and cabbage‐containing diet for the next 7 days, and (3) the control diet for the 10 subsequent days. Antipyrine and phenacetin were administered orally before breakfast on days 7 and 10, respectively, of each dietary regimen. During the test diet period the mean plasma half‐life of antipyrine decreased 13% and the mean metabolic clearance rate increased 11%. While small, these changes were statistically significant, indicating a stimulatory effect of cabbage and brussels sprouts on antipyrine metabolism. The values returned to control levels during the second control diet period. During the test diet period the mean plasma concentration of phenacetin was decreased by 34% to 67% at each time interval from 0.5 to 7 hr after phenacetin administration, and the mean plasma concentration of total (conjugated plus unconjugated) N‐acetyl‐p‐aminophenol (APAP), phenacetin's major metabolite, was increased from 0.5 to 3 hr after phenacetin administration. The concentrations of phenacetin and APAP returned toward control values during the second control diet period. The mean plasma half‐life of phenacetin was not influenced by the dietary changes. These results suggest that the test diet enhanced the metabolism of phenacetin in the gastrointestinal tract and/or during its first pass through the liver. Feeding the test diet increased the mean ratio of conjugated APAP to unconjugated APAP observed in plasma at each time interval from 0.5 to 7 hr after phenacetin administration, suggesting that the diet enhanced the conjugation of APAP.

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The present work tests the hypothesis that high fat/low carbohydrate diets elevate the level of liver microsomal cytochrome P450IIE1. Male Sprague-Dawley rats were fed liquid diets containing varied ratios of corn oil/carbohydrate for 4 d. Rats fed diets with higher fat/carbohydrate ratios produced higher serum acetone levels and higher hepatic microsomal P450IIE1 content and N-nitrosodimethylamine demethylase activity than those fed diets with lower fat/carbohydrate ratios. This dietary fat/carbohydrate effect on P450IIE1 also was observed with modified semipurified AIN-76A diets. In addition, both the quantity and the extent of unsaturation of dietary lipids affected P450IIE1 regulation. At moderate fat levels (5 and 20% diet), rats fed corn oil and menhaden oil diets produced higher P450IIE1 activity than those fed lard and olive oil diets. Rats fed a diet containing 20% corn oil or an amount of linoleic acid equivalent to the 20% corn oil diet showed twofold to threefold increases in the level of P450IIE1 over those fed a fat-free diet. Rats fed a 25% corn oil diet showed twofold higher enflurane metabolism in vivo than those fed a 0.5% corn oil diet. The present results suggest that the constitutive P450 enzyme level is regulated by dietary fat/carbohydrate ratios.

Eight healthy volunteers were sequentially fed a control diet, a charcoal-broiled beef--containing diet, and the control diet a second time. The mean plasma half-lives (t1/2) of antipyrine and theophylline were each decreased by 22% after the subjects were fed the charcoal-broiled beed--containing diet. The main plasma t1/2s for these drugs returned to control values when the subjects were fed the control diet for a second time. Considerable individuality occurred in the responsiveness of the subjects to the charcoal-broiled beef--containing diet. The decreases in antipyrine plasma t1/2s among the 8 subjects ranged from 5% to 39%, and the decreases in theophylling t1/2s ranged from 0% to 42%.

Ten healthy subjects were fed three diets for 10 days each: a control diet, a cabbage and brussels sprouts--containing diet, and the control diet a second time. Oxazepam was taken on day 7 and acetaminophen on day 10 of each dietary regimen. The test diet stimulated the metabolism of acetaminophen, at least in part by enhanced glucuronidation, as evidenced by a 16% decrease in mean plasma AUC, a 17% increase in mean metabolic clearance rate, an increased ratio of acetaminophen glucuronide to acetaminophen in plasma from 1 to 11 hr after drug and an 8% increase in mean 24-hr urinary recovery of acetaminophen glucuronide, which returned toward control when the subjects were fed the control diet a second time. There were no comparable changes in the metabolism of acetaminophen to acetaminophen sulfate. When the subjects ate the test diet, 24-hr urinary recovery of the cysteine conjugate and of 3-methoxyacetaminophen sulfate, end-products of minor oxidative pathways, the former involving a toxic intermediate, decreased 13% and 22%. Cabbage and brussels sprouts induced a 17% decrease in mean plasma AUC and a 19% increase in mean metabolic clearance rate for oxazepam, but there was no change in mean plasma t1/2 for this drug, nor was there a change in ratio in plasma of oxazepam glucuronide to oxazepam.

Unlabelled BACKGROUND. Changes in the sympathetic nervous system may be a cause of postoperative cardiovascular complications. The authors hypothesized that changes in both beta-adrenergic receptor (betaAR) function (as assessed in lymphocytes) and in sympathetic activity (assessed by plasma catecholamines and by heart rate variability [HRV] measurements obtained from Holter recordings) occur after operation. Methods The HRV parameters were measured in 28 patients having thoracotomy (n = 14) or laparotomy (n = 14) before and for as long as 6 days after operation. Transthoracic echocardiography was performed before and on postoperative day 2. Lymphocytes were also isolated from blood obtained before anesthesia and again on postoperative days 1, 2, 3, and 5 (or 6). They were used to examine betaAR number (Bmax) and cyclic adenosine monophosphate (cAMP) production after stimulation with isoproterenol and prostaglandin E1. In addition, plasma epinephrine, norepinephrine, and cortisol concentrations were determined at similar intervals. Results After abdominal and thoracic surgery, most time and all frequency indices of HRV decreased significantly, as did Bmax and basal and isoproterenol-stimulated cAMP production. The decrements in HRV correlated with those of Bmax and isoproterenol-stimulated cAMP throughout the first postoperative week and inversely correlated with the increase in heart rate. Plasma catecholamine concentrations did not change significantly from baseline values, but plasma cortisol levels did increase after operation in both groups. Left ventricular ejection fraction was normal in both groups and unaffected by surgery. Conclusions Persistent downregulation and desensitization of the lymphocyte betaAR/adenylyl cyclase system correlated with decrements in time and frequency domain indices of HRV throughout the first week after major abdominal or thoracic surgery. These physiologic alterations suggest the continued presence of adaptive autonomic regulatory mechanisms and may explain why the at-risk period after major surgery appears to be about 1 week or more.

Fentanyl administered epidurally to parturients after cesarean delivery has a primarily spinal mechanism of action and this effect is enhanced by very small dose epidural bupivacaine and epinephrine.

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