Pharmacokinetics of Phenobarbitone in Protein Energy Malnutrition

Abstract

Phenobarbitone kinetics was studied in malnourished and normal children after single oral dose of approximately 7.0 mg/kg. Estimation of serum phenobarbitone concentration was performed by spectrophotometric method. Elimination half-life was 58.9 ± 9.5 h and 30.15 ± 6.1 h for malnourished and healthy children, respectively. Compared to healthy children, t(max) was prolonged in malnutrition group suggesting slow absorption in the latter group. The systemic bioavailability was observed to be higher in protein energy malnutrition. Modifications of the usual dosage regimen in malnutrition arc recommended.

A systematic review of pharmacokinetics studies in children with protein-energy malnutrition

“…Other drugs that are primarily metabolised by the liver had increased half-lives in association with PEM [28,29,31,54] This was probably because most of these drugs are rarely metabolised as they are known to be eliminated unchanged via the kidneys [61]. Decreased total clearance was, however, demonstrated for two drugs [19,47,53] and in view of the small number of drugs studied (six), it is impossible to draw firm conclusions about the effect of PEM on renal drug elimination.…”

“…Other drugs that are primarily metabolised by the liver had increased half-lives in association with PEM [28,29,31,54], although their clearances were not reported. This would suggest that lower doses or alternatively less frequent administration of drugs in PEM may be required.…”

“…One to 17 blood samples were collected from individual children. Table 1 shows the effect of PEM on absorption of 18 drugs [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. The extent of absorption of most of the drugs (10) was not significantly affected.…”

“…There were 11 studies where the plasma half-life was calculated without any clearance values (Table 6) [15,17,20,23,25,28,29,31,32,54,55]. Five studies documented an increase in the plasma half-life of five separate drugs whereas the other studies showed no significant effect of PEM on the plasma half-life of the remaining six drugs.…”

Pathophysiological changes that affect drug disposition in protein-energy malnourished children

“…Plasma albumin and fractions of the glycoproteins responsible for binding drugs are decreased [43-45]. As a result of this decreased protein binding, in theory, there may be a substantial increase in the plasma free-drug fractions of highly protein-bound drugs and children with PEM may experience variations in their response to drug treatment or be at risk of increased drug toxicity [46].…”