Influence of Glucose (&lt;i&gt;in vivo&lt;/i&gt; or &lt;i&gt;in vitro&lt;/i&gt;) on Duration of Narcotic Analgesics and on the Kinetics of Drug Metabolism

Strother, A.; Chau, Lucille S.K.

doi:10.1159/000137428

Cited by 13 publications

(7 citation statements)

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“…In some studies, carbohydrates reduced the metabolism of drug substrates in vivo and in vitro without affecting microsomal protein or total CYP content. 24,25) A number of findings in the present study suggest that the mechanism of down-regulation of liver CYP mRNA expression by fat-free TPN involves multiple factors related to the metabolism of fatty acids, including nuclear receptors. 26,27) The findings of the present study clearly demonstrated the usefulness of soybean oil as a lipid source in the hyperalimentation solution for TPN in the infant rat model.…”

Section: Discussionmentioning

confidence: 63%

Soybean Oil Fat Emulsion Prevents Cytochrome P450 mRNA Down-Regulation Induced by Fat-Free Overdose Total Parenteral Nutrition in Infant Rats

Yamaguchi

Yamauchi

Nishimura

et al. 2005

Biological & Pharmaceutical Bulletin

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In total parenteral nutrition (TPN), which is also known as parenteral hyperalimentation, all of the patient's daily nutritional requirements are supplied by infusing nutrients directly into the systemic circulation. TPN is widely employed in a variety of pathophysiological settings for the nutritional support of patients with conditions requiring complete bowel rest (e.g., some stages of Crohn's disease, ulcerative colitis, and severe pancreatitis) or pediatric patients with gastrointestinal disorders (e.g., congenital anomalies and protracted nonspecific diarrhea). In particular, TPN therapy is essential for low-birth-weight neonates and infants with inflammatory bowel disease or Crohn's disease. However, it has been recognized that the excessive administration of fat-free TPN is associated with the development of cholestasis 1) and hepatic steatosis, 2) which can be fatal in neonates or infants who do not receive oral feeding for a prolonged period. In addition to such pathophysiological abnormalities, hepatic drug metabolizing activity is markedly affected by fat-free TPN in humans 3) and rats. 4) Knodell et al. reported that 7-d parenteral infusion of a hyperalimentation solution containing glucose, amino acids, and electrolytes via the jugular vein led to a decrease in cytochrome P450-mediated oxidative metabolism in rats.4) Thus, TPN therapy without fat may affect the pharmacokinetics of therapeutic drugs and eventually induce adverse events in patients.The hepatic cytochrome P450 (CYP) isoenzymes are involved in the detoxification of endogenous and exogenous compounds for further metabolism or elimination. Therapeutic drugs are mainly metabolized by the CYP1, CYP2, and CYP3 isoenzymes in the CYP families.5) The CYP4 family has been shown to be related to the metabolism of fatty acids.6) Since the capacity of CYP-mediated drug metabolism in the neonate or infant is lower than that in the adult, 7,8) severe adverse reactions may occur in pediatric patients if additional pharmacotherapy is required during fat-free TPN therapy. It is therefore important to elucidate the specific changes in the hepatic CYP isoenzymes during fat-free TPN in the neonate or infant and to clarify the effects of including fat in the TPN regimen. However, to the best of our knowledge, there have been no reports in the literature focusing on the changes in hepatic CYP isoenzymes during TPN therapy.Intravenous fat emulsions, especially soybean oil, are now available as a source of essential fatty acids in patients receiving TPN, and "three-in-one" solutions containing a mixture of amino acids, glucose, and lipid have been found to be clinically safe, stable, and economical. However, there has been some controversy regarding the possible advantages of including fat in the TPN regimen. Some studies have found that intravenous fat infusion can improve hepatic dysfunction, 9) but others have reported that it may induce hepatic steatosis and progressive cholestasis in humans 10) and rats. 11)We have recently developed an infant rat model ...

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Section: Discussionmentioning

confidence: 63%

Soybean Oil Fat Emulsion Prevents Cytochrome P450 mRNA Down-Regulation Induced by Fat-Free Overdose Total Parenteral Nutrition in Infant Rats

Yamaguchi

Yamauchi

Nishimura

et al. 2005

Biological & Pharmaceutical Bulletin

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“…The data presented clearly show an in crease in the duration of barbiturate anesthe sia (ST) by glucose treatment in the rat, with out significant changes in microsomal pro tein and P450 content, as was also pre viously found in mice [Strother et al, 1971;Peters and Strother, 1972;Strother and Chau, 1980], The small but significant de crease in the glycogen levels in rat liver mi crosomes is in agreement with previous find ings in the rat [Wools and McPhillips, 1966;Fouts et al, 1961;Hartshorn et al, 1974] but was not seen in the mouse [Strother et al, 1971]. Dixon et al [ 1964] found that hepatic microsomal enzyme activity and glycogen content were not well correlated.…”

Section: Discussionmentioning

confidence: 73%

“…Previous studies [Strother et al. 1971 ;Peters and Strother, 1972;Strother and Chau, 1980] with mice have shown that glucose treatment inhibits the metabolism of type 1 substrates e.g. p-nitroanisole, hexobarbital and methadone.…”

Section: Discussionmentioning

confidence: 99%

“…Such changes could be the explanation for the effect of glucose treat ment on ST in rats and mice and on the kinetic parameters (apparent Km and Vmax) for the microsomal mediated metabolism of hexobarbital and methadone in mice [Peters and Strother, 1972;Strother and Chau, 1980], Several mechanism may be possible for these changes in the kinetics of substrate binding and metabolism by hepatic micro somal P450.…”

Section: Discussionmentioning

confidence: 99%

“…The analgesic effects of morphine and methadone were also significantly extended when mice were allowed to drink a 30% glu cose solution in place of water for 48 h. The glucose pretreatment also resulted in a reduc tion of the in vitro metabolism of meperidine and methadone by the hepatic 9,000-g super natant fraction [Strother and Chau, 1980] and kinetic analysis of the methadone data indi cated an increase in the apparent Km and a decrease in the apparent Vmax. These results suggested that glucose treatment may produce a mixed type (competitive, noncompetitive) of inhibition of the hepatic (in vitro) metabo lism of methadone.…”

Section: Introductionmentioning

confidence: 97%

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Effect of Glucose Administration on Various Rat Hepatic Constituents and on the Spectral Binding of Hexobarbital and Methadone to Rat Hepatic Cytochrome P450

Buchholz¹,

Strother²,

Fraser³

1989

Pharmacology

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The administration of glucose to rats for 48 h resulted in an increase in the duration of anesthesia produced by intraperitoneal injection of pentobarbital. The effect of this glucose treatment on hepatic glycogen and on microsomal protein, cytochrome P450 (P450), cholesterol, lipid and phospholipid content, as well as on the spectral binding of hexobarbital and methadone to microsomal P450, was examined. The glucose treatment appeared to have no effect on microsomal protein or P450 content. The binding of hexobarbital and methadone by P450 produced a type 1 spectrum in both control and glucose-treated animals. The glucose treatment resulted in a decrease in the spectral dissociation constant (K_s) and in the maximal spectral binding (ΔA_max) of hexobarbital to P450 while with methadone there was an increase in Ks and a decrease in ΔA_max. Total lipid, phosphatidylcholine and phosphatidylethanolamine were increased in the microsomal fractions from glucose-treated animals. The changes in the parameters for drug binding to microsomal P450 probably relate to the increased lipid content of the microsomes although changes in the proportion of P450 isoenzymes could be involved. The previously observed decrease in the microsomal metabolism of hexobarbital and methadone following glucose treatment may be due to decreased binding of these compounds to microsomal P450.

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Glucose alters rat liver S9-mediated mutagenesis, metabolism and DNA-binding of aflatoxin B1

Teel¹,

Strother²

1990

Cancer Letters

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Influence of Glucose (<i>in vivo</i> or <i>in vitro</i>) on Duration of Narcotic Analgesics and on the Kinetics of Drug Metabolism

Cited by 13 publications

References 1 publication

Soybean Oil Fat Emulsion Prevents Cytochrome P450 mRNA Down-Regulation Induced by Fat-Free Overdose Total Parenteral Nutrition in Infant Rats

Soybean Oil Fat Emulsion Prevents Cytochrome P450 mRNA Down-Regulation Induced by Fat-Free Overdose Total Parenteral Nutrition in Infant Rats

Effect of Glucose Administration on Various Rat Hepatic Constituents and on the Spectral Binding of Hexobarbital and Methadone to Rat Hepatic Cytochrome P450

Glucose alters rat liver S9-mediated mutagenesis, metabolism and DNA-binding of aflatoxin B1

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