Pharmacokinetics of Phenobarbital During Certain Enhanced Elimination Modalities to Evaluate Their Clinical Efficacy in Management of Drug Overdose

Abstract

This work was performed to study the pharmacokinetics of phenobarbital during renal clearance enhancement, intestinal clearance enhancement, and a combination of both to determine which method is clinically more effective in the management of drug poisoning. Thirty young patients with phenobarbital overdose were enrolled in the study. They were classified according to the method of treatment to enhance the elimination of phenobarbital into three equal groups: those treated with multiple-dose activated charcoal (MDAC) alone; those treated with urinary alkalinization alone; and those treated with a combination of the two methods. All patients received the required supportive care at the same time as the elimination procedures. Plasma phenobarbital levels were determined on admission and at 6, 12, 18, 24, 30, 36, 42, and 48 hours after admission by the enzyme multiplied immunoassay technique. The results showed that the decrease in plasma phenobarbital levels with MDAC was significantly greater than with either urinary alkalinization or the combined use of both. The results also revealed statistically significant greater total body clearance for phenobarbital and consequently a shorter half-life with MDAC treatment versus either urinary alkalinization alone or the combined use of both. Thus, the authors conclude that the management of drug overdose in the case of weak acidic drugs that have small volumes of distribution should include the sole use of MDAC and supportive care, without urinary alkalinization.

Successful haemofiltration therapy in severe phenobarbital overdose

“…There have been multiple case reports regarding successful extracorporeal treatment in severe barbiturate intoxication. 3,4,6,[9][10][11][12][13][14] Haemodialysis involves solute removal by diffusion whereas haemofiltration uses convection with hydrostatic pressure inducing plasma water filtration across the haemofilter. 6 Haemoperfusion is ideal in the removal of lipid soluble or highly protein bound drugs.…”

Successful use of haemodialysis to treat phenobarbital overdose

“…The advent of more superior haemodialysis machines calls for a review of the use of haemodialysis as a treatment modality for phenobarbital overdose. Haemodialysis is most effective for drugs with a low molecular weight, high water solubility and small volume of distribution, which is true of phenobarbital, with volumes of distribution reported at 0.54–0.9 L/kg 3 4…”

Toxicology Today

“…23 Urine alkalinization enhances elimination of phenobarbital and may be used in conjunction with multiple doses of activated charcoal which increases clearance rate. 24,25 Other than in the setting of the previously mentioned poisonings, urinary alkalinization is not recommended.…”