Tissue concentration, systemic distribution and toxicity of clofazimine--an autopsy study.

There are very few autopsy studies available on systemic distribution of clofazimine, a drug with anti-mycobacterial activity, used in multidrug therapy (MDT) regimen of leprosy and in erythema nodosum leprosum (ENL). An autopsy study was done on a 45 year old female of lepromatous leprosy (LL) on MDT and long term high dosage of clofazimine. Patient succumbed to intractable abdominal pain, diarrhoea, hypokalemia following clofazimine treatment. Autopsy study revealed yellowish brown discoloration of skin, viscera and body fluids. Chemical extraction of the drug revealed the highest concentration of the drug in jejunum (1.5mg/gm),followed by spleen (1.2mg/gm), pancreas (0.4mg/gm), adrenal (0.25mg/gm), liver (0.21mg/gm), and less than 0.2mg/gm in lung, fat, large intestine and stomach. It can be inferred from the present study that the drug is absorbed from the jejunum and gets deposited in fat, reticulo-endothelial cells (R-E cells) and hepatocytes. The drug is best demonstrated in cryostat sections and is lost partly during tissue processing and staining. The drug toxicity can be fatal as seen in the present case.

Renal parameters during infancy.

In a prospective study we estimated common renal parameters in 48 full term normal neonates, of which 15 were also tested at 6 months and 12 months of age. The mean levels of serum creatinine, were high at birth (0.73 mg/dl) but normal for age at 6 and 12 months; uric acid followed a similar trend. The blood pH and bicarbonate were low at birth (7.28 and 20.36 mEq/L, respectively) reached normal adult values by 12 months; chloride levels were high at birth (110 +/- 5 mEq/L) and normal at 6 months. The plasma renin activity was higher than normal all throughout the first year (27.1, 416.8, 64.8 ng/ml/hr by RIA). Plasma aldosterone values were high at birth (1387.5 pg/ml) and reached normal level (301.6) at 12 months. Renal length and volume as assessed by ultrasonography compared well with American standards. Urinary constituents were variable due to breast feeding up to 6 months and varied diet during the weaning period. This study shows that mild metabolic acidosis and hyperchloremia due to immaturity of renal acidification mechanism and high renin and aldosterone levels due to partial nonresponsiveness of distal tubules are normal variables in babies from birth to 6 months. The levels of serum creatinine and uric acid are high at birth and in assessing renal functions this should be borne in mind.