Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of food and gastric acidity on the bioavailability of ketoconazole tablets were investigated in 12 volunteers using a six-treatment, randomized, Latin-square crossover design. All volunteers received all treatments, as follows: (A) ketoconazole 200 mg administered after a fast; (B) ketoconazole 200 mg with a standardized high-fat meal; (C) ketoconazole 200 mg with a standardized high-carbohydrate meal; (D) ketoconazole 200 mg after pretreatment with glutamic acid hydrochloride 680 mg as capsules; (E) ketoconazole 200 mg in a simulated achlorhydric state induced with cimetidine and sodium bicarbonate; and (F) ketoconazole 200 mg administered with glutamic acid hydrochloride in a simulated achlorhydric state. Ketoconazole concentrations were measured by high-performance liquid chromatography in plasma samples drawn immediately before and at various times over 24 hours after drug administration. Bioavailability variables, including natural logarithm transformation for area under the concentration-time curve (AUC), were subjected to analysis of variance followed by Duncan's Multiple Range testing. Treatments B and C significantly prolonged the times required to achieve the peak plasma ketoconazole concentration, and treatment C also significantly reduced the peak plasma ketoconazole concentration (Cmax) compared with treatment A. There was a trend toward increased AUC values with treatment B and decreased AUC values with treatment C. Treatment D produced a higher Cmax compared with treatment A, and treatment E produced large, significant reductions in Cmax and AUC values compared with treatment A. Treatment F significantly increased AUC values and Cmax compared with treatment E.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of food and gastric acidity on absorption of orally administered ketoconazole. 335 20

Ketoconazole appears to be an effective prophylactic measure in surgical patients at risk of developing ARDS. The beneficial effects may be caused by thromboxane synthetase inhibition because thromboxane B2 concentrations were decreased by ketoconazole in both studies. Two studies were unable to demonstrate a beneficial effect with the selective thromboxane synthetase inhibitor dazoxiben. Both studies consisted of a small number of subjects with already established ARDS, not prophylaxis in patients at risk of ARDS. Although the effects of ketoconazole on mortality in patients at risk of ARDS are conflicting, there may be reduced mortality in patients with sepsis. Several issues must be considered before ketoconazole is used in this setting. First, the studies to date have excluded patients at risk of hepatotoxicity, which is probably wise considering the potential hepatotoxicity with ketoconazole and the unknown benefit/risk ratio in these patients. Also, therapies that reduce gastric acidity should be avoided to ensure bioavailability. If ketoconazole is administered through a jejunostomy tube, it probably should be given with a dilute acid to enhance absorption. Furthermore, ketoconazole is a known inhibitor of the cytochrome P450 system, which results in a number of drug interactions. If ketoconazole is used, the patient's current drug therapy should be reviewed for potential interacting drugs. In light of the current studies, ketoconazole may be considered for surgical patients at risk of developing ARDS (especially patients with sepsis) with the previously noted considerations. Future research should seek to confirm ketoconazole's role for the prevention of ARDS in all critically ill patients. Additional studies also should clarify the role of various inflammatory mediators in the pathophysiology and therapy of ARDS.
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PMID:Ketoconazole to prevent acute respiratory distress syndrome in critically ill patients. 852 99