Phenobarbital pharmacokinetics

TR Browne, JE Evans, GK Szabo, BA Evans, DJ Greenblatt. Studies with stable isotopes. II. phenobarbital pharmacokinetics during monotherapy. J din Pharmacol 25 51—58, 1985. 

PitUck W, Painter M, Pippenger C. Phenobarbital pharmacokinetics in neonates. CUn Pharmacol Ther 1978 23 346-350. 

Kuranari M, TatsukawaH, SeikeM, SaikawaT, Ashikari Y, Kodama Y, Sakata T,Takeyama M. Effect of phenytoin on phenobarbital pharmacokinetics in a patient with epilepsy. Ann Pharmacother 99S) 29, 83-4. 

Dispositional antagonism occurs when one drug alters the pharmacokinetics (absorption, distribution, biotransformation, or excretion) of a second drug so that less of the active compound reaches the target tissue. Tor example, phenobarbital induces the biotransformation of warfarin, reducing its anticoagulant activity... 

Pharmacokinetics Primidone is readily absorbed from the Gl tract. Phenobarbital appears in plasma after several days of continuous therapy. Therapeutic plasma concentrations are 5 to 12 mcg/mL for primidone and 15 to 40 mcg/mL for phenobarbital. PEMA and phenobarbital have longer half-lives (10 to 18 hours and... 

Pharmacokinetics PO route onset 20-60 min, peak N/A, duration 6-8 hr. Well absorbed after PO administration. Widely distributed. Metabolized in liver to active metabolite, a form of phenobarbital. Minimally excreted in urine. Removed by hemodialysis. Half-life 34 hr. 

Clozapine is metabolized by hepatic CYP 1A2 and, to a lesser degree, CYP 3A3/4 therefore, the drug is subject to changes in serum concentration when combined with medications that inhibit or induce these enzymes. Serum clozapine levels increase with coadministration of fluvoxamine or erythromycin and decrease with coadministration of phenobarbital or phenytoin and with cigarette smoking (Byerly and DeVane 1996). These pharmacokinetic interactions are particularly important because of the dose-dependent risk of seizures. 

For pharmacokinetics, drug interactions, and toxicity of phenobarbital, see Chapter 22. 

Being one of the long-time standards in basic psychopharmacology, there are few major variants to the procedure apart from the kind of barbiturate employed. Several barbiturates undergo clear hepatic metabolism, for example pentobarbital and phenobarbital, thereby confounding interpretations because of pharmacokinetic and metabolic factors. Indeed, one modification of the method has been specifically employed to estimate enzyme induction in the liver as indicated by more rapid barbiturate metabolism. Animals given a pre-exposure to a test substance are then exposed to a standard dose of phenobarbital (80 mg/kg i.p.) 24 hours later and assessed for sleep duration. The presence or absence of a decrease in sleep duration is taken as an index of the hepatic enzyme induction produced by the test substance (Kushikata et al. 2003). 

Colburn WA (1981) Simultaneous pharmacokinetic and pharmacodynamic modeling. J Pharmacokin Biopharm 9 367 Dingemanse J, Van Bree JB, Danhof M (1989) Pharmacokinetic modeling of anticonvulsant reponse of Phenobarbital in rats. J Pharmacol Exp Ther 249 601-608 Hoffman A, Goldberg A (1994) The relationship between receptor-effector unit heterogeneity and the shape of the concentration-effect profile pharmacodynamic implications. J Pharmacokinet Biopharm 22 449-468... 

The major route of elimination is hepatic metabolism. The variability in the metabolism and pharmacokinetics in neonates, infants and children necessitates monitoring of drug concentrations in the plasma, particularly when it is co-administered with phenytoin, phenobarbital or rifampin. 

Figure 2.20. Pharmacokinetic parameters and stractures of cimetidine and phenobarbital...

The effects of other antiepileptic drugs on the pharmacokinetics of lamotrigine have been studied in 62 patients with epilepsy (71). Carbamazepine, phenytoin, and phenobarbital, all enzjme inducers, increased the oral clearance of lamotrigine, individually by 58% and in combination by nearly 200%. 

Duran S H, Ravis W R, Pedersoli W M et al 1987 Pharmacokinetics of phenobarbital in the horse. American Journal of Veterinary Research 48 807-810 Evans M S. Reid K H, Sharp J B 1993 Dimethylsulfoxide (DMSO) blocks conduction in peripheral nerve C fibers a possible mechanism of analgesia. Neuroscience Letters 150 145... 

Pharmacokinetics of phenobarbital in horses after single and repeated oral administration of the drug. American Journal of Veterinary Research 53 706-710... 

Ravis W R, Duran S H, Pedersoli W M et al 1987 A pharmacokinetic study of phenobarbital in mature horses after orai dosing. Journal of Veterinary Pharmacology and Therapeutics 10 283-289... 

Spear A M, Hill M R, Mayhew I G et al 1984 Preliminary study on the pharmacokinetics of phenobarbital In the neonatal foal. Equine Veterinary Journal 16 368-371... 

Phenobarbital (Luminal) Schedule IV Route Pregnancy Pharmacokinetic Well-... 

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