T.C. Raghuram

Pharmacokinetics of tetracycline in nutritional oedema

Tetracycline pharmacokinetics were studied in a group of normal subjects and in patients with nutritional oedema. Though both groups of subjects received similar dose per kilogram body weight, plasma concentrations and area under the curve (AUC) were significantly higher in nutritional oedema patients. The total body clearance of the drug was reduced due to significant reductions in renal and non-renal clearance of drug. The volume of distribution (VB) was low, with significant increase in rate of transfer of drug from peripheral to central compartment (K21), indicating poor tissue sequestration of the drug in nutritional-oedema patients. In some respects, these alterations in kinetics of tetracycline in nutritional-oedema patients are different from our earlier observations made in undernourished subjects who had mild and moderate forms of malnutrition. These results suggest that changes in disposition of drugs are also influenced by the severity of malnutrition, and demand suitable alterations in dosage regimen.

Accidental Acute Fatal Sodium Nitrite Poisoning

An accidental food poisoning outbreak occurred resulting in the death of 14 of the 22 affected persons. Chemical analysis of food materials revealed the presence of sodium nitrite and potassium arsenate. Analysis of urine, gastric contents, liver and kidney, collected at the time of autopsy, confirmed the presence of these chemical substances in high concentrations. Epidemiological data indicated that the food poisoning occurred due to the accidental use of sodium nitrite and potassium arsenate instead of table salt in the preparation of tamarind (Tamarindus indica) soup.

Effect of leucine and isoleucine on brain serotonin concentration in rats

Excess dietary leucine can deplete the brain of its serotonin (5HT) content. Simultaneous isoleucine supplement can counteract the effect of leucine. Nicotinic acid and nicotinamide incorporation into the diet at physiological levels can also reverse leucine effects. These results are discussed in relation to altered mental function seen in endemic pellagra.

Antipyrine kinetics in undernourished diabetics

SummaryIn developing countries diabetics frequently suffer from varying grades of malnutrition. The combined effect of malnutrition and non-insulin dependent diabetes (NIDDM) on the drug metabolising enzyme system has been evaluated using antipyrine as a protodrug. All the patients were under treatment and their plasma glucose values were within normal limits.The AUC of antipyrine was similar in all the groups. Although none of the kinetic parameters was altered in normal diabetics, the clearance of antipyrine was decreased and its half life was prolonged, with an increase in volume of distribution, in undernourished diabetics compared to undernourished controls. The results indicate that diabetes per se may not influence antipyrine kinetics when the blood glucose is well under control, but in the presence of undernutrition, it significantly alters the disposition of the drug.

Influence of nutritional status on plasma levels and relative bioavailability of tetracycline

SummaryRelative bioavailability after oral administration of a single dose and Cmin levels of tetracycline in plasma after multiple doses were determined in groups of well-nourished and undernourished subjects. The relative bioavailability of tetracycline, assessed by the area under serum concentration time-curves, did not differ in undernourished and well-nourished patients. The plasma levels were not different in the two groups after the conventional dose of tetracycline HCl 250 mg at 6 hour intervals. However, in these studies undernourished subjects received a higher dose per kg body weight, which could have compensated for any effect of a shortened half life of the drug. When the dose per kg body weight was reduced, the Cmin levels were lower. On the other hand, with the same dose per kg body weight at more frequent intervals, the plasma concentrations were similar to those in well-nourished subjects. These studies indicate that the dosage regimen should be based both on body weight and on the nutritional status of the individual.

Influence of dietary restriction and protein deficiency on plasma half-life and tissue distribution of tetracycline in rats.

The effects of dietary restriction and protein deficiency on plasma half‐life and tissue distribution of tetracycline were studied in rats by feeding either a 20% protein diet in restricted quantity or a 9% protein diet ad lib and compared with rats given a 20% protein diet ad lib (control group).