Aminopyrine—an effective modifier of liver and serum gamma glutamyl transpeptidase

Bartels, H.; Hauck, W.; Vogel, Ingeborg

doi:10.1016/s0022-3476(75)80494-x

Cited by 22 publications

(3 citation statements)

References 16 publications

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“…In particular, greater GGT activity was seen in all of the patients, whereas increases in ALP, ALT, and/or AST activity occurred in a far lower proportion. Other studies of children or infants of nursing mothers given these antiepileptics have similarly shown increases, most consistently in serum GGT, and more variably in other serum hepatobiliary marker enzymes (Bartels et al 1975; de Wolff et al 1982; Frey et al 2002; Merlob et al 1992). The incidence of the serum enzyme increases among immature subjects across these studies tended to be greater than that reported in adults on comparable regimens of these antiepileptics (Table 5).…”

Section: Hepatic Metabolic Enzyme Induction and Associated Clinical Pmentioning

confidence: 77%

“…However, the predominance of GGT increases over other laboratory changes, and the magnitude of change in all of the serum enzymes evaluated (typically three-fold reference values in the absence of other findings supportive of hepatic injury) were generally similar between children and adults in these reports ( Table 5). The predominance of increases in GGT over changes in other serum enzymes with administration of potent CYP3A4 inducers has also been supported by findings in humans given rifampicin (Bartels et al 1975;Ellis et al 1979;Perucca et al 1988). Further, correlation analyses between serum enzymes in a few of these clinical studies have demonstrated no association between GGT and ALP and only an occasional association between GGT and ALT (Acheampong-Mensah 1976;Deutsch et al 1986;Haidukewych and John 1986;Sano et al 1981;Tutor et al 1988).…”

Section: Hepatobiliary Biomarker Findings In Association With Prototymentioning

confidence: 91%

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Effects of Hepatic Drug-metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man

et al. 2010

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Hepatic drug-metabolizing enzyme (DME) induction is an adaptive response associated with changes in preclinical species; this response can include increases in liver weight, hepatocellular hyperplasia and hypertrophy, and upregulated tissue expression of DMEs. Effects of DME induction on clinical pathology markers of hepatobiliary injury and function in animals as well as humans are not well established. This component of a multipart review of the comparative pathology of xenobiotically mediated induction of hepatic metabolizing enzymes reviews pertinent data from retrospective and prospective preclinical and clinical studies. Particular attention is given to studies with confirmation of DME induction and concurrent evaluation of liver and/or serum hepatobiliary marker enzyme activities and histopathology. These results collectively indicate that in the rat, when histologic findings are limited to hepatocellular hypertrophy, DME induction is not expected to be associated with consistent or substantive changes in serum or plasma activity of hepatobiliary marker enzymes such as alanine aminotransferase, alkaline phosphatase, and gamma glutamyltransferase. In the dog and the monkey, published studies also do not demonstrate a consistent relationship across DME-inducing agents and changes in these clinical pathology parameters. However, increased liver alkaline phosphatase or gamma glutamyltransferase activity in dogs treated with phenobarbital or corticosteroids suggests that direct or indirect induction of select hepatobiliary injury markers can occur both in the absence of liver injury and independently of induction of DME activity. Although correlations between tissue and serum levels of these hepatobiliary markers are limited and inconsistent, increases in serum/plasma activities that are substantial or involve changes in other markers generally reflect hepatobiliary insult rather than DME induction. Extrahepatic effects, including disruption of the hypothalamic-pituitary-thyroid axis, can also occur as a direct outcome of hepatic DME induction in humans and animals. Importantly, hepatic DME induction and associated changes in preclinical species are not necessarily predictive of the occurrence, magnitude, or enzyme induction profile in humans.

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Section: Hepatic Metabolic Enzyme Induction and Associated Clinical Pmentioning

confidence: 77%

Section: Hepatobiliary Biomarker Findings In Association With Prototymentioning

confidence: 91%

Effects of Hepatic Drug-metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man

et al. 2010

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“…The increase of liver GGT activity is accompanied by a more moderate enhancement of the microsomal drug metabolizing enzyme system as reflected by the increase of the terminal oxidase cytochrome P-450 thus suggesting a drug-mediated microsomal enzyme induction rather than microso-ma1 injury. Similar changes of rat liver GGT can be achieved by the administration of aminopyrine and phenobarbitone, the effect of the latter drug being less pronounced than that of phenytoin and of aminopyrine (Idho et al 1971, Bartels et al 1975).…”

Section: Resultsmentioning

confidence: 91%

Significance of Increased Serum Gamma-Glutamyltransferase Activity during Long-Term Anticonvulsive Treatment. Clinical and Experimental Studies^1,2

Bartels¹,

Evert²,

Hauck³

et al. 1975

Neuropediatrics

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Significance of increased serum gamma-glutamyltransjerase activity during long-term anticonvulsive treatment. Clinical and experimental studies. Neuropadiatrie 6: 77-89 (1975). In epileptic children on anticonvulsive treatment for at least 4 weeks, the following laboratory tests were performed and compared to age matched controls: serum activity determinations of gamma-glutamyltransferase (GGT), alanine (GPT) and aspartate aminotransferases, leucin arylamidase (LAP), alkaline phosphatase (AP), glutamate dehydrogenase (GLDH), and cholinesterase (CHE), determinations of fibranogen and clotting factors II, V, and VII, and of urinary D-glucaric acid excretion. Serum GGT activity was increased up to about 10 times above the upper limit of normal range (x + 2s) in 83 of 103 children, AP was enhanced in 26, CHE in 21, GLDH in 20, and GPT in 14 children (p< .05). Except for AP, the frequency of other increased serum activities was raised according to the degree of GGT enhancement. Clotting factor V was moderately elevated in 21°/o of those children, who had enhanced GGT activities (p < .05), no further significant deviation of any of the clotting factors was observed. In 17 children so studied the serum GGT activity was closely correlated to the urinary excretion of D-glucaric acid, an indicator of microsomal enzyme activity (r= + 0.67, p < .01). In phenytoin treated rats, given 100 mg/kg and 300 mg/kg, respectively, daily for 17-25 days, a dose dependent enhancement of liver and serum GGT was measured. This occured predominantly in total liver and in liver microsomes, less marked in the soluble liver fraction and in serum. An elevation of microsomal cytochrome P-450 in the liver was also found. It is concluded, that isolated enhancement of serum GGT activity during anticonvulsive treatment is not indicative of liver damage, but rather, of a clinically insignificant elevation of microsomal enzymes. Increased blood levels of other so-called liver enzymes and of clotting factors may be suggestive of more complex alterations of liver metabolism, the pattern of the laboratory findings being indicative of a clinically latent disturbance of excretory functions of the hepatobiliary system rather than of hepatic parenchymal damage. Enhancement of serum AP activity is primarily due to a disturbance in calcium metabolism.

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The Effect of Rifampicin on Plasma Glutamyl Transpeptidase, Salicylamide Glucuronide Formation and D-Glucaric Acid Excretion

Katzos

Sotiriu

et al. 1976

Pharmacology of Antibiotics

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Aminopyrine—an effective modifier of liver and serum gamma glutamyl transpeptidase

Cited by 22 publications

References 16 publications

Effects of Hepatic Drug-metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man

Effects of Hepatic Drug-metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man

Significance of Increased Serum Gamma-Glutamyltransferase Activity during Long-Term Anticonvulsive Treatment. Clinical and Experimental Studies^1,2

The Effect of Rifampicin on Plasma Glutamyl Transpeptidase, Salicylamide Glucuronide Formation and D-Glucaric Acid Excretion

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Aminopyrine—an effective modifier of liver and serum gamma glutamyl transpeptidase

Cited by 22 publications

References 16 publications

Effects of Hepatic Drug-metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man

Effects of Hepatic Drug-metabolizing Enzyme Induction on Clinical Pathology Parameters in Animals and Man

Significance of Increased Serum Gamma-Glutamyltransferase Activity during Long-Term Anticonvulsive Treatment. Clinical and Experimental Studies1,2

The Effect of Rifampicin on Plasma Glutamyl Transpeptidase, Salicylamide Glucuronide Formation and D-Glucaric Acid Excretion

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Significance of Increased Serum Gamma-Glutamyltransferase Activity during Long-Term Anticonvulsive Treatment. Clinical and Experimental Studies^1,2