Phenobarbital Diphenylhydantoin

Rapid Method for Simultaneous Determination of Phenobarbital, Diphenylhydantoin and Their Main Hydroxylated Metabolites by Nitrogen-Selective Gas Chromatography... 

In humans, administration of o,p -DDD [l,l-dichloro-2-(4-chlorophenyl)-2-(2-chlorophenyl) ethane], phenobarbital, diphenylhydantoin, or phenylbutazone causes a marked elevation in the urinary excretion of 6 )5-hydroxycortisol presumably by accelerating the metabolism of glucocorticoids. Accordingly, treatment of animals with phenobarbital stimulates the hydroxylation by hepatic microsomes of corticosterone, deoxycorticosterone, cortisone, and cortisol, whereas 3-methylcholanthrene has negligible effect on the hydroxylation of cortisone or cortisol. The physiological consequences of this induction, however, remain obscure. 

Proceeding along a parallel track, Guillory and coworkers used DTA analysis to study complexation phenomena [2]. Through the performance of carefully designed studies, they were able to prove the existence of association complexes and deduced the stoichiometries of these. In this particular work, phase diagrams were developed for 2 1 deoxycholic acid-menadione, 1 1 quinine-phenobarbital, 2 1 theophylline-phenobarbital, 1 1 caffeine-phenobar-bital, and 1 1 atropine-phenobarbital. The method was also used to prove that no complexes were formed between phenobarbital and aspirin, phenacetin, diphenylhydantoin, and acetaminophen. 

Phenobarbital, frons-stilbene oxide, diallyl sulfide, diphenylhydantoin, amitriptyline induce CYP2B1 and CYP2B2 mRNA in rat striatum and cerebellum (Schilter et al., 2000). 

CI2. Cucinell, S. A., Conney, A. H., Sansor, M., and Bums, J. J., Drug interactions in man lowering effect of phenobarbital on plasma levels of dicoumarol and diphenylhydantoin. Clin. Pharmacol. Thcr. 6, 420-429 (1965). 

K20. Kupferberg, H. J., Quarrtitative estimation of diphenylhydantoin, primidone and phenobarbital in plasma by gas-liquid chromatography. Clin. Chim. Acta 29, 283-288 (1970). 

V2. Van Meter, J. C., Buckmaster, H. S., and Shelley, L. L., Concurrent assay of phenobarbital and diphenylhydantoin in plasma by vapour-phase chromatography. Clin. Chem. 16, 135-138 (1970). 

Phenytoin is the oldest nonsedative antiseizure drug, introduced in 1938 after a systematic evaluation of compounds such as phenobarbital that altered electrically induced seizures in laboratory animals. It was known for decades as diphenylhydantoin. 

Pulse polarography has also been used to measure dantrolene in plasma [181] and trimethoprim [192] and nitroimidazoles in blood [193,194]. The overall recovery of the trimethoprim assay was reported to be 81.7 6.3% (SD) with a detection limit of 0.5-0.75 fxg/mL of blood. There was no interference from the sulfamethoxazole, which is administered simultaneously. Glibomuride [195], phenobarbital, and diphenylhydantoin [97] have all been determined as their nitro derivatives after extraction from blood. The recovery of phenobarbital and diphenylhydantoin from blood was 72.3 6.5% (SD) and 76.6 2.3% (SD), respectively, with a detection limit of 1-2 fxg/mL. A modified assay [97] for the determination of both compounds in blood with TLC separation was also described. A differential pulse polarography determination of cephalosporin antibiotics in human serum samples has recently been described [196]. 

Long-term anticonvulsive therapy with diphenylhydantoin or phenobarbital is known to cause osteomalacia by influencing calcium metabolism (24,25). Alteration in the metabolism of vitamin D, presumably secondary to induction of hepatic microsomal enzymes, leads to the calcium and bone abnormalities (26). Patients on anticonvulsive therapy with phenytoin exhibit a decrease in serum 25-hydroxyvitamin D (27). Adequate dietary amounts of vitamin precursors or microsomal enzyme stimulators might prevent these effects of long-term therapy. 

Another early example of the use of LC was in the analysis of diphenylhy-dantoin and phenobarbital levels in the plasma of a patient receiving these drugs for the management of epilepsy (25,26). As shown in Figure 2-29, by using LC the plasma was found to contain 8.5 fig of phenobarbital and 9.2 fig of diphenylhydantoin per milliliter. The LC method, additionally, has several advantages over other methods. These advantages include faster separation, lack of derivatization, better sample stability, and smaller sample size (25,26). 

Brunk, S.D. Hadjiioannou, T.P. Hadjiiannou, S.I. Malmstadt, H.V. Adaptation of emit technique for serum phenobarbital and diphenylhydantoin assays to miniature centrifugal analyzer. Clin. Chem. 1976, 22, 905-907. 

Drugs that are the most common cause of TEN are allopurinol, ampicillin, amoxicillin, carbamazepine, NSAIDs, phenobarbital, pentamidine, phenytoin (diphenylhydantoin), pyrazolones, and sulfonamides. 

Peraino, C., Fry, R. J., Staffeldt, E., and Christopher, J. P. (1975). Comparative enhancing effects of phenobarbital, amobarbital, diphenylhydantoin, and dichlorodiphenyltrichloroethane on 2-acetylami-nofluorene-induced hepatic tumorigenesis in the rat. Cancer Res 35(10), 2884—2890. 

Morselli PL, Rizzo H Garattini S. Interaction between phenobarbital and diphenylhydantoin in animals and in epileptic patients. Ann NYAcadSci (1971) 179,88-107. 

Cucinell SA, Conney AH, Sansur H Bums JJ. Drug interactions in man I. Lowerm effect of phenobarbital on plasma levels of bishydroj coumarin (Dicumarol) and diphenylhydantoin QDilantin). Clin Pharmacol Ther (1965) 6,420-9. 

Buchanan R Heffelfmger JC, Weiss CP. The effect of phenobarbital on diphenylhydantoin metabolism in children Pediatrics (1969) 43,114-16. 

Kutt H, Hawes J, Verebely K, McDowell F. The effect of phenobarbital on plasma diphenylhydantoin level andmetabolism in man andrat liver microsomes. Neurology (1969) 19,611-16. 

GarrettsonLK, Dayton PG. Disappearance of phenobarbital and diphenylhydantoin from serum of children. Clin Pharmacol Ther ( 910) 11,674-9. 

Kristensen H Hansen JH Skovsted L. The influence of phenobarbital on the half-life of diphenylhydantoin in man. Acta Med Scand (1969) 185,347-50. 

Diamond WD, Buchanan RA. A clinical study of the effect of phenobarbital on diphenylhydantoin plasma levels. J Clin Pharmacol (1970) 10,306-11. 

Booker HE, Tormey A, Toussaint J. Concurrent administration of phenobarbital and diphenylhydantoin lack of an interference effect. Neurology (1971) 21,383-5. 

Wilson JT, Wilkinson GR. Chronic and severe phenobarbital intoxication in a child treated with primidone and diphenylhydantoin. J Pediatr (1973) 83, 484-9. 

Johannessen SI, Strandjord RE, Munthe-Kaas AW. Lack of effect of clonazepam on serum levels of diphenylhydantoin, phenobarbital and carbarnazepine. Acta Neurol Scand (1977) 55, 506-12,... 

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