Metabolism of sulphadiazine in malnutrition.

Abstract

1. The kinetics of sulphadiazine were studied in well‐nourished and under‐nourished subjects. 2. The metabolic clearance rate of a single dose of sulphadiazine given either orally or intravenously was faster in under‐nourished subjects. 3. The plasma protein binding of the drug was found to be reduced in under‐nourished subjects. 4. Blood concentrations (48 h and 72 h) of sulphadiazine tended to be low in the under‐nourished as compared with well‐nourished subjects after administration of multiple doses of the drug. 5. It is concluded that a revision in the dosage schedule may not be necessary in the treatment of under‐nourished subjects with sulphadiazine, since the blood concentrations were higher than the reporte d minimum to combat infection.

Kinetics of sulphafurazole in undernutrition.

“…Several reports from this Institute and elsewhere have shown a difference in the kinetics of drugs in the undernourished subjects as compared to the wellnourished (Shastri & Krishnaswamy 1976;Mehta et al, 1975;Shastri & Krishnaswamy 1979;Krishnaswamy & Naidu 1977). Data presented here are different.…”

“…Evidently, SFZ does not seem to follow this general law, for in spite of a lowered protein binding of the drug found in the undernourished subjects, the rate of acetylation was not altered as seen by values of the acetyl SFZ in urine. That the capacity to acetylate SFZ by the liver in the undernourished is impaired seems unlikely for, as reported earlier (Shastri & Krishnaswamy, 1979) the acetylation of sulphadiazine occurred in the undernourished at a rate faster than normal. On the other hand, the results observed here seem to suggest that the renal excretory mechanism seems to overwhelm the capacity of the liver to eliminate the drug by acetylation, even though a greater proportion of the drug seems to exist in an unbound form in the undemourished subjects.…”

“…Data presented here are different. It is interesting to note that whereas single dose kinetic studies with sulphadiazine (Shastri & Krishnaswamy, 1979) showed a difference in the (Weinstein, 1975). In spite of a plasma protein binding of 85%, the drug has a short half-life because of a high renal clearance (Cohen & Pocelinko, 1973).…”

“…Earlier studies (Shastri & Krishnaswamy, 1979) reported from this Institute indicated that the half-life of sulphadiazine was shortened in undernourished adult subjects. Sulphadiazine is not highly bound to plasma protein, unlike some other sulphur compounds, which are highly protein bound.…”

“…In recent years there have been a number of reports on the influence of malnutrition on drug metabolism in man (Shastri & Krishnaswamy, 1976;Krishnaswamy & Naidu, 1977;Mehta, Kalsi, Jayaraman & Mathur, 1975; Shastri & Krishnaswamy, 1979;Homeida, Karrar & Roberts 1979). These studies have emphasised the importance of considering nutritional status in the planning of therapeutic regimen.…”