Phenobarbitone elimination

Repeated dose of activated charcoal administered by oral route have been shown to enhance the non-renal elimination of carbamazepine, salicylates, phenobarbitone, phenytoin, digoxin, theophylline and meprobamate. In severe cases activated charcoal is to be administered via a nasogastric tube. 

Penicillins and cephalosporins have short half-lives (0.5-1.5 h) in domestic animals because these antibiotics are secreted by the proximal renal tubules and, due to their high degree of ionization, are not reabsorbed from the distal nephron. The half-lives of lipid-soluble weak organic acids (e.g. sulphadi-methoxine, sulphadiazine, phenobarbitone) and organic bases (e.g. trimethoprim, procainamide, amphetamine) of which a significant fraction (> 20%) of the dose is eliminated by renal excretion may be influenced by the urinary pH reaction. Under acidic urinary conditions, which are normally present in carnivorous species, weak acids are reabsorbed from the distal renal tubules, whereas the excretion of weak bases is enhanced. 

As the induction of hepatic microsomal oxidative activity by a lipid-soluble drug (e.g. phenobarbitone) or xenobiotic could decrease the duration of action of therapeutic agents that are mainly eliminated by microsomal oxidation, the effect of induction would be considered a form of biochemical antagonism. Drug-induced inhibition of microsomal oxidative activity, without adjustment of dosage of a concomitantly administered therapeutic agent that undergoes extensive hepatic metabolism, could lead to toxicity. Cimetidine, ketoconazole and chloramphenicol inhibit hepatic microsomal enzyme activity. 

Most cases of poisoning are treated conservatively, i.e. the symptoms arc treated and the drug is eliminated by nonnal metabolism and renal excretion. When there is hepatic or renal insufficiency, active measures such as haemodialysis or charcoal haemoperfusion may be attempted.. Such measures are normally restricted to a small group of drugs and poisons including salicylate, phenobarbitone. theophylline, ethanol, methanol, ethylene glycol and lithium. Where active measures are used to eliminate drugs, plasma concentrations should be monitored. 

Fig. 1 Elimination of phenytoin and phenobarbitone from plasma at different rates.

Bodin has applied direct argentimetric potentiometric titration to phenobarbitone and its sodium salt in preparations containing a variety of standard diluents. He eliminates uncertainty in the end-point potential by determining the potential of a standard blank solution (saturated with silver carbonate) for each sample just prior to titration and using this as the end-point potential for titration of the sample. Stearates, halides and ammonium salts interfere and special consideration must be given to samples containing polyethylene glycols, alcohol, or hexamine. He includes a procedure for removal of stearates from tablets. 

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