6 children with protein calorie nalnutrition (PCM) and 5 control children received a single dose of sulfadiazine (25 mg/kg body weight). Absorption rate constant in the control group was 0.735 ± 0.058 h^–1 and in PCM 0.519 ± 0.03 h^–1. Peak blood levels of the drug were similar in both groups. However, the time to reach the peak was shorter in the control than in the PCM group. Elimination rate constant and half life of the drug were 0.0233 ± 0.0026 h-¹ and 31.78 ± 3.82 h, respectively, in the PCM group and 0.0332 ± 0.0022 h^-1 and 21.27 ± 1.51 h, respectively, in the control group. These values differ significantly from each other. The area under the blood concentration-time curve was more than double in the PCM group as compared to the control group. Urinary excretion of the drug in 48 h was significantly more in control (19.3 ± 1.4 mg/kg body weight) in comparison to the PCM group (13.6 ± 1.7 mg/kg body weight). However, the free drug concentration in urine/kg body weight was not altered in the PCM group. There was a significant decrease in quantity of acetylated drug in the PCM group as compared to the controls. In view of these observations, therapy with sulfadiazine in children suffering from PCM requires reconsideration.

Plasma half-life and metabolic clearance rate of antipyrine administered intravenously in a dose of 16 mg/kg body weight was studied in 10 children suffering from protein calorie malnutrition and five normal children matched in age and sex. Plasma half-life was increased and metabolic clearance rate was decreased in malnourished children (10.4 hr and 47.1 ml/hr per kg, respectively) in comparison to controls (6.3 hr and 70.1 ml/hr per kg, respectively). This observation indirectly reflects the lowered activity of microsomal oxidative enzyme of liver. Five children were restudied after nutritional rehabilitation of 17 to 25 days. Antipyrine plasma half-life decreased to 6.6 hr and metabolic clearance rate increased to 66.5 ml/hr per kg. These values were similar to those in normal children indicating biological recovery. The drug therapy in children with protein calorie malnutrition requires reconsideration in light of these observations.

The plasma levels and urinary excretion of chloramphenicol was studied in ten malnourished children and four normal children after oral administration of a single dose of 25 mg/kg body weight. Plasma peak levels were achieved 2-4 hours later and were 1.5 or 2 times higher in malnourished children compared to the normal. They also took much longer to clear the drug from the plasma, 30 hours or more in malnourished children compared with 12 hours in the normal. These observations point to a slower rate of biotransformation in the liver. The excretion pattern of the drug and its metabolite lends support to this hypothesis. 75-85% of the drug excreted was in the form of conjugated fraction in the normal while only 35-55% was conjugated in malnourished children. In two children the liver biopsy tissue was subjected to assay of bilirubin-UDP transferase and low levels were detected. This observation also points to an alteration in the rate of biosynthesis of chloramphenicol.

Hepatic drug metabolism in patients with acute viral hepatitis was investigated under different conditions: pregnancy, postpartum, non-pregnancy, and among males. Liver function tests were altered in all of these conditions. The relationship between in vivo and in vitro drug metabolism was studied in twenty-two patients using diagnostic liver needle biopsies by comparing the drug metabolising enzymes (aminopyrine-N-demethylase and bilirubin-UDP-glucuronyl transferase) in these biopsies with the elimination kinetics of antipyrine. Drug clearance tests were repeated in the patients who had recovered. All patients gave altered liver function tests results. Antipyrine half-life was significantly higher in females as compared to males. Among females, it was maximum in the pregnant group. Activities of drug metabolising enzymes were found to be significantly lower in liver biopsy material. The half-life of antipyrine showed a significant correlation with drug metabolising enzymes. After recovery patients showed a normal antipyrine half-life.

The pharmacokinetics of intravenous chloramphenicol has been studied in 42 patients with liver disease and in 8 controls. The half-life of chloramphenicol (t 1/2) was increased in the various liver disorders, the metabolic clearance rate (MCR) and apparent volume of distribution (Vd) were decreased and the area under the time - concentrations curve (AUC) showed an increase. The t 1/2 of chloramphenicol showed a significant correlation with serum albumin and prothrombin time index.