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Biomedical subjects

J R Saha

Publications and source records attributed to J R Saha.

17 recordsLinked to original sources
PubMed1988

Interethnic variation in the metabolic inactivation of digoxin by the gut flora.

Digoxin is metabolized to cardioinactive reduced metabolites (digoxin reduction products) in some patients by anaerobic bacteria present in the gut flora. We compared the tendencies of Americans and Bangladeshis to reduce digoxin by this pathway. Of 97 normal Americans in New York City, 34 (35.1%) were metabolizers in contrast to 14 of 100 Bangladeshis in Dhaka (p less than 0.002). Forty-three (35.8%) of 120 American patients in New York City receiving digoxin reduced the drug compared with 4 (13.8%) of 29 Bangladeshi patients in Dhaka (p less than 0.05). In Americans who emigrated to Dhaka or Bengali immigrants to New York City, the frequency of digoxin reduction product excretion was that of their country of origin. Fourteen Bengali immigrants who were nonmetabolizers when first studied in New York did not metabolize digoxin when restudied 4 yr later. In the Bangladeshis studied in Dhaka, income, education, and most strongly, urban residence during childhood correlated positively with digoxin inactivation. The findings are consistent with the hypothesis that the metabolic functions of the anaerobic gut flora may be determined by environmental factors operative early in life and tend to remain stable in adulthood. Interethnic variations in drug metabolism may be the consequence of differences in the intestinal microflora.

Adolescent↗
PubMed1987

Digoxin inactivation by the gut flora in infancy and childhood.

Inactivation of digoxin by reduction of the lactone ring has recently been shown to occur in one third of adults and to be mediated by anaerobic intestinal bacteria. Children from birth through adolescence were studied to determine the pattern of development of this gut flora-mediated process. None of 36 digitalized infants 8 months of age or less excreted reduced digoxin metabolites in the urine. The adult pattern of digoxin reduction product excretion by one third of patients was observed after 16 months of age; however, high levels of digoxin reduction products such as are found in 10% of adults were not encountered in children less than 9 years of age. Even though reduced metabolites were not formed in vivo early in life, stool cultures of 20 of 73 infants younger than 8 months of age contained digoxin reduction product-forming bacteria at high concentrations, in some instances as early as the second week of life. Maturation of the gut flora with respect to digoxin metabolism appears to be a protracted process. The relative digoxin resistance of infants and children is not due to bacterial inactivation.

Adolescent↗
PubMed1983

Digoxin-inactivating bacteria: identification in human gut flora.

Digoxin, the most widely used cardiac glycoside, undergoes significant metabolic conversion in many patients to cardioinactive metabolites in which the lactone ring is reduced. This appears to occur within the gastrointestinal tract. An attempt was made to isolate and identify the organisms capable of reducing digoxin from stool cultures obtained from human volunteers. Of hundreds of isolates studied, only Eubacterium lentum, a common anaerobe of the human colonic flora, converted digoxin to reduced derivatives. Such organisms were also isolated in high concentrations from the stools of individuals who did not excrete these metabolites when given digoxin in vivo. When the growth of E. lentum was stimulated by arginine, inactivation of digoxin was inhibited. Neither the presence of these organisms alone nor their concentration within the gut flora appeared to determine whether digoxin would be inactivated by this pathway in vivo.

Arginine↗
PubMed1983

Decreased digoxin cardioinactive-reduced metabolites after administration as an encapsulated liquid concentrate.

The generation by intestinal bacteria of large amounts of cardioinactive metabolites of digoxin with a reduced lactone ring (digoxin reduction products, or DRP) may be associated with increased dosage requirements. Since DRP excretion varies inversely with bioavailability, we compared the 6-day urinary excretion (CUE) of digoxin and DRP after 0.4-mg doses of an encapsulated liquid concentrate and a standard tablet in 22 normal subjects known to form substantial amounts of DRP. Mean (+/- SE) CUE of digoxin was greater with the capsules than the tablets (195.9 +/- 8.6 and 137.5 +/- 6.3 micrograms). CUE of DRP was less after the capsules (60.8 +/- 5.5 and 102.7 +/- 9.5 micrograms). Percent DRP was greater after the tablets in every subject (mean for tablets, 41.2 +/- 2.7%; capsules, 23.5 +/- 1.8%). Patterns of DRP excretion differed with the two preparations, probably reflecting differences in the routes whereby digoxin reached the colon. The use of highly bioavailable capsules in subjects with heavy DRP production should minimize metabolic inactivation during digoxin therapy.

Adult↗
PubMed1982

Inactivation of digoxin by Eubacterium lentum, an anaerobe of the human gut flora.

Digoxin is converted to cardioinactive reduced metabolites (DRP) in vivo and in vitro by the human gut flora. Digoxin inactivation is mediated by Eubacterium lentum, a normal inhabitant of the gastrointestinal flora. E. lentum appears to be the sole organism performing this reaction. Fecal bacteria that convert digoxin to DRP in vitro have been found to be present in some subjects who fail to make DRP in vivo. DRP-forming E. lentum have been isolated from the stools of two such subjects. When increasing amounts of arginine are supplied as a growth substrate to E. lentum, bacterial growth and DRP production vary inversely. Further study will be required to identify the factors which determine why digoxin is inactivated in vivo by the gut flora of certain patients and not by others.

Adult↗
PubMed1981

Inactivation of digoxin by the gut flora: reversal by antibiotic therapy.

In approximately 10 per cent of patients given digoxin, substantial conversion of the drug to cardioinactive, reduced metabolites (digoxin reduction products, or DRPs) occurs. The site and clinical importance of this conversion is unknown. In four normal volunteers taking digoxin daily for four weeks, urinary excretion of DRPs was greatest after a poorly absorbed tablet was ingested, and least after intravenous administration, Stool cultures from subjects known to make DRPs in vivo ("excretors") converted digoxin to DRPs; cultures from nonexcretors did not. Three excretors were given tablets for 22 to 29 days. A five-day course of erythromycin or tetracycline, administered after a base-line period of 10 to 17 days, markedly reduced or eliminated DRP excretion in urine and stool. Serum digoxin concentrations rose as much as twofold after antibiotics were given. We conclude that in some persons digoxin is inactivated by gastrointestinal bacteria. Changes in the enteric flora may markedly alter the state of digitalization.

Anti-Bacterial Agents↗