Plasma transaminase

In other respects, the adverse effects of cerivastatin are similar to those of other statins (3), and a pooled analysis of studies of cerivastatin 100-400 micrograms/day taken for at least 8 weeks showed no differences in drug-related adverse events between cerivastatin and placebo (4). There was no association between plasma transaminase or creatine kinase activities and cerivastatin dosages. 

A number of studies have measured the activation of plasma transaminases by pyridoxal phosphate added in vitro however, it is difficult to interpret the results, because plasma transaminases arise largely accidentally, as a result of cell turnover, and the amount released will depend on tissue damage. Furthermore, there is a considerable amount of pyridoxal phosphate in plasma, largely associated with serum albumin, and the extent to which plasma transaminases are saturated will depend largely on the relative affinity of albumin and the enzyme concerned for the coenzyme, rather than reflecting the availability of pyridoxal phosphate for intracellular metabolism. Studies on erythrocyte transaminase activation coefficient are easier to interpret, because the extent to which the enzymes are saturated depends mainly on the availability of pyridoxal phosphate. 

UNTOWARD EFFECTS Erythromycin rarely causes serious side effects. Allergic reactions include fever, eosinophUia, and rash, either alone or in combination these manifestations resolve after therapy is stopped. Cholestatic hepatitis, the most striking side effect, is caused primarily by erythromycin estolate and rarely by the ethylsuccinate or the stearate and may be a hypersensitivity reaction to the estolate ester. The illness starts after 1-3 weeks of treatment and presents with nausea, vomiting, and abdominal cramps. These symptoms soon are followed by jaundice, fever, leukocytosis, eosinophilia, and elevated plasma transaminases. Liver biopsy reveals cholestasis and periportal inflammation, sometimes with necrosis of neighboring parenchymal cells. Findings usually resolve within a few days after drug cessation and rarely are prolonged. 

Centrilobular hepatic necrosis by single doses of coumarin (1,2-benzopyrone, ds-o-coumarinic acid lactone) have been reported in the rat (Lake 1984, Lake et al. 1989, Fentem et al. 1992), whereas chronic administration resulted in bile duct lesions (Hagan etal. 1967, Cohen 1979, Evans etal. 1989). The mechanism of acute coumarin-induced hepatotoxicity in the rat has been investigated by comparing the effects of coumarin with those of a number of methyl-substituted coumarin derivatives (Lake etal. 1994). Coumarin administration produced dose-related hepatic necrosis and a marked elevation of plasma alanine aminotransferase and aspartate aminotransferase activities. In contrast, non of the coumarin derivatives examined produced either hepatic necrosis or elevated plasma transaminase activities. Coumarin reduced hepatic microsomal ethylmorphine N-demethylase and 7-ethoxycoumarin 0-deethylase activities, whereas one or both mixed function oxidases appeared to be induced by treatment with 3,4-dimethylcoumarin, 4-methylcoumarin, 3-methyloctahydrocoumarin and 4-methyloctahydrocoumarin. These results provides an evidence that acute coumarin-induced hepatotoxicity in the rat is due to the formation of a coumarin 3,4-epoxide intermediate. 

Synergistic hepatotoxicity of N,N-dimethylformamide and carbon tetrachloride was examined. Treatment of rats with either DMF or CCI4 resulted in small increase in plasma transaminases and lactate dehydrogenase activities, but combined treatment with both solvents markedly increased blood biochemical changes. Single dose of CCI4 enhances liver toxicity of DMF. ... 

The initial enthusiasm for tacrine and velnacrine, which are the anticholinesterases most studied clinically, has been tempered by the fact that not all patients respond. Most show the peripheral parasympathomimetic effects of cholinesterase inhibition, e.g. dyspepsia and diarrhoea, as well as nausea and vomiting, and about half of the patients develop hepatotoxicity with elevated levels of plasma alanine transaminase. While some peripheral effects can be attenuated with antimuscarinics that do not enter the brain, these add further side-effects and the drop-out rate from such trials is high (<75%) in most long-term studies. Donepezil appears to show less hepatotoxicity but its long-term value remains to be determined. 

Chronic copper poisoning in domestic sheep is first characterized by a period of passive accumulation of copper in the tissues. This period varies from a few weeks to more than a year. During this time the animal appears outwardly normal although the liver may contain more than 1000 mg Cu/kg DW and plasma activities of aspartate transaminase, sorbitol dehydrogenase, lactic... 

After 48 h, marked increase in blood glucose, depressed plasma insulin level, marked depletion of liver glycogen, significant increase in plasma creatinine phosphokinase and glutamic oxaloacetic transaminase activity (Giri etal. 1979)... 

Ketoconazole inhibits a variety of cytochrome P450 enzymes, including 11-hydroxylase and 17-hydroxylase. It is highly effective in lowering cortisol in Cushing s disease, and patients can be maintained successfully on therapy for months to years. The most common adverse effects are reversible elevation of hepatic transaminases and GI upset. It can cause gynecomastia and lower plasma testosterone values. 

The aminotransferases, aspartate transaminase and alanine transaminase, are enzymes that have increased concentrations in plasma following hepatocellular injury. The highest concentrations are seen in acute viral infections, or ischemic or toxic liver injury. 

Peptides in Human Urine (Skarzynski and Samecka-Keller), 5, 107 Protein Bound Iodine (Chaney), I, 82 Radioactive Iodine-131 in the Diagnosis of Hyperthyroidism, Blood Plasma Levels of (Silver), 1, 111 Transaminase Activities of Serum and Body Fluids, the Clinical Significance of Alterations in (Wroblew-ski), 1, 314... 

Recently we have evaluated several exogenous and endogenous tests of liver function in rainbow trout following intoxication by the model hepatotoxicant CCl. The results of these studies indicate that elevated plasma activity of the enzyme glutamate-pyruvate transaminase (GPT) is the most sensitive endogenous index of... 

The liver is also the principal metabolic center for hydrophobic amino acids, and hence changes in plasma concentrations or metabolism of these molecules is a good measure of the functional capacity of the liver. Two of the commonly used aromatic amino acids are phenylalanine and tyrosine, which are primarily metabolized by cytosolic enzymes in the liver [1,114-117]. Hydroxylation of phenylalanine to tyrosine by phenylalanine hydroxylase is very efficient by the liver first pass effect. In normal functioning liver, conversion of tyrosine to 4-hy-droxyphenylpyruvate by tyrosine transaminase and subsequent biotransformation to homogentisic acidby 4-hydroxyphenylpyruvic acid dioxygenase liberates CO2 from the C-1 position of the parent amino acid (Fig. 5) [1,118]. Thus, the C-1 position of phenylalanine or tyrosine is typically labeled with and the expired C02 is proportional to the metabolic activity of liver cytosolic enzymes, which corresponds to functional hepatic reserve. Oral or intravenous administration of the amino acids is possible [115]. This method is amenable to the continuous hepatic function measurement approach by monitoring changes in the spectral properties of tyrosine pre- and post-administration of the marker. 

Transient abnormalities in liver function tests (eg, elevation in serum bilirubin, alkaline phosphatase, serum transaminases), and reduced biliary excretion of contrast media used for visualization of the gallbladder have also been observed. Drug/Food interactions Food interferes with the absorption of rifampin, possibly resulting in decreased peak plasma concentrations. Take on an empty stomach with a full glass of water. 

Dyspepsia is the most common side effect of zileuton. Liver transaminase levels are elevated in a small percentage of patients taking zileuton. Serum Uver transaminase levels should be monitored and treatment halted if significant elevations occur. Zileuton inhibits the metabolism of theophylline. Thus, when these agents are used concomitantly, the dose of theophylline should be reduced by approximately one-half, and plasma concentrations of theophylline should be monitored closely. Caution should also be exercised when using zileuton concomitantly with warfarin, terfenadine, or propranolol, as zileuton inhibits the metabolism of these agents. Zileuton is contraindicated in patients with acute liver disease and should be used with caution in patients who consume substantial quantities of alcohol or have a history of liver disease. 

Transient, mild increases in liver enzyme levels, up to three times the upper limit of normal, do not necessitate discontinuation of valproate. Although y-glutamyltransferase levels are often checked by clinicians, these levels are often increased, without clinical significance, in patients receiving valproate and carbamazepine (Dean and Penry 1992). Likewise, plasma ammonia levels are often increased transiently during valproate treatment, but this finding does not necessitate interruption of treatment (Jaeken et al. 1980). Increases in transaminase levels are often dose dependent. If no... 

Vigabatrin Irreversibly inhibits GABA-transaminase 70% bioavailable not bound to plasma proteins not metabolized, ti/2 5-7 h (not relevant because of mechanism of action) Partial seizures, infantile spasms Toxicity Drowsiness, dizziness, psychosis, visual field loss Interactions Minimal... 

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