Malnutrition and drugs: clinical implications.

Elimination kinetics determined by a timed plasma concentration curve on chloramphenicol, antipyrine, acetaminophen and sulphadiazine showed that plasma half-life was increased and elimination rate constant was diminished in malnourished children compared to those with normal nutrition. Area under the curve (AUC) was increased. Decreased urinary excretion of metabolites of chloramphenicol and sulphadiazine in malnourished children suggested an alteration in biotransformation. These findings were supported by a significant increase in steady-state levels of chloramphenicol and phenobarbitone in malnourished patients receiving drugs for therapy. In a subhuman primate animal model (young rhesus monkey) which was akin to the human situation both for protein energy malnutrition and for drug pharmacokinetics it was observed that hepatic aminopyrine demethylase and chloramphenicol glucuronyl transferase activity was diminished. Thus drugs metabolised by the liver apparently clear at a slower pace in malnourished children. Therapy needs to be modified appropriately to achieve therapeutic response and avoid toxicity. Hepatotoxicity monitoring of antitubercular therapy with isoniazid and rifampicin was found to be 3 times higher in malnourished children. The acetylator status of the child did not correlate with hepatotoxicity. The majority of the children were slow acetylators. AUC of isoniazid was higher in malnourished children.