Pharmacokinetic variability of phenobarbital: a systematic review of population pharmacokinetic analysis

Clinical pharmacology and dosing regimen optimization of neonatal opioid withdrawal syndrome treatments

“…95 It is metabolized primarily by CYP2C9, and by CYP2C19 and CYP2E1 to a lesser | 1241 PHARMACOLOGY OF NOWS TREATMENTS extent. 95,97 About 20%-40% of the drug is excreted through the kidney, and renal excretion is dependent on urine flow and pH. 95,97 Clearance of phenobarbital can be affected by age, disease states, and certain concomitant drugs.…”

“…95,97 About 20%-40% of the drug is excreted through the kidney, and renal excretion is dependent on urine flow and pH. 95,97 Clearance of phenobarbital can be affected by age, disease states, and certain concomitant drugs. 95 In adults, phenobarbital clearance is about 0.004-0.006 L/h/kg, with a half-life of ranging from 70 to 140 h. 94,95,97,98 PKs in neonates Although very high bioavailability is observed in adults, one study reported the bioavailability of oral phenobarbital in neonates and young infants to be ~48.9%.…”

“…95,97 Clearance of phenobarbital can be affected by age, disease states, and certain concomitant drugs. 95 In adults, phenobarbital clearance is about 0.004-0.006 L/h/kg, with a half-life of ranging from 70 to 140 h. 94,95,97,98 PKs in neonates Although very high bioavailability is observed in adults, one study reported the bioavailability of oral phenobarbital in neonates and young infants to be ~48.9%. 99 Plasma binding in neonates is lower than in infants/children and adults, and conversely neonates have slightly higher volumes of distribution (~0.9-1 L/kg) than the latter.…”

“…A review of these studies is available elsewhere. 97 Briefly, a one-compartment structure was used in all studies included (likely due to sparse sampling), and three most commonly identified predictors of clearance were weight, age, and concomitant anti-epileptic drugs (phenytoin, carbamazepine, or valproic acid). 97 A summary of neonatal and adult PK parameters and phenobarbital elimination is presented in Figure 5.…”

“…118 This approach not only can result in more efficient individualized dosing, but also can provide flexibility in clinical sampling for TDM (e.g., non-steady-state concentrations). 97 When applying population PK models, one needs to keep in mind that the modeling results often need to be interpreted within the context of their specific study population. For example, two published population PK models of clonidine in pediatric patients incorporating PNA on weight-standardized clearance yielded different prediction of clearance maturation trajectory, likely due to difference in age composition of the studied population.…”