Abstract
Clonazepam (1 mg/kg) and antipyrine (0.1 mg/kg) were administered simultaneously by intravenous bolus injection to three dogs. After 2 weeks of chronic phenobarbital administration, the studies were repeated. Plasma concentration-time curves in all studies were biexponential. Phenobarbital administration increased total plasma clearances of clonazepam and antipyrine by 102% and 98.5%, respectively. Volumes of distribution were not altered, and consequently reductions in terminal exponential half-lives observed after phenobarbital were attributed to increases in clearances.
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M. A. Schwartz, C. W. Williams, and A. S. Leon. Metabolic profile of clonazepam-2-14C in the man, dog and rat. Report on file, Hoffmann-La Roche, Nutley, N.J. 07110.
E. Eschenhof. Untersuchungen über das Schicksal des Antikonvulsivums Clonazepam im Organismus der Ratte, des Lundes und des Menschen.Arzneimittel-Forsch. 23:390–400 (1973).
S.A. Kaplan, K. Alexander, M. L. Jack, C. V. Puglisi, J. A. F. de Silva, T. L. Lee, and R. E. Weinfeld. Pharmacokinetic profiles of clonazepam in dog and humans and of fiunitrazepam in dog.J. Pharm. Sci. 63:527–532 (1974).
C. Y. Huang, J. G. McLeod, D. Sampson, and W. J. Hensley. Clonazepam in the treatment of epilepsy.Med. J. Aust. 2:5–8 (1974).
F. E. Dreifuss, J. K. Penry, S. W. Rose, H. J. Kupferberg, P. Dyken, and S. Sato. Serum clonazepam concentrations in children with absence seizures.Neurology 25:255–258 (1975).
A. Berlin and H. Dahlström. Pharmacokinetics of the anticonvulsant drug clonazepam evaluated from single oral and intravenous doses and by repeated oral administration.Eur. J. Clin. Pharmacol. 9:155–159 (1975).
O. Sjö, E. F. Hvidberg, J. Naestoft, and M. Lund. Pharmacokinetics and side-effects of clonazepam and its 7-aminometabolite in man.Eur. J. Clin. Pharmacol. 8:249–254 (1975).
H. J. Knop, E. van der Kleijn, and L. C. Edmunds.Pharm. Weekblad. 110:297–309 (1975).
S. A. Cucinell, R., Koster, A. H. Conney, and J. J. Burns. Stimulatory effect of phenobarbital on the metabolism of diphenylhydantoin.J. Pharmacol. Exp. Ther. 141:157–160 (1963).
A. H. Conney and K. Schneidman. Enhanced androgen hydroxylase activity in liver microsomes of rats and dogs treated with phenylbutazone.J. Pharmacol. Exp. Ther. 146:225–235 (1964).
S. A. Cucinell, A. H. Conney, M. Sansur, and J. J. Burns. Drug interactions in man. I. Lowering effect of phenobarbital on plasma levels of bishydroxycoumarin (dicumarol) and diphenylhydantoin (dilantin).Clin. Pharmacol. Ther. 6:420–429 (1965).
R. M. Welch, Y. E. Harrison, A. H. Conney, and J. J. Burns. An experimental model in dogs for studying interactions of drugs with bishydroxycoumarin.clin. Pharmacol. Ther. 10:817–825 (1969).
J. R. Gillette, J. J. Kamm, and H. A. Sasame. Mechanism ofp-nitrobenzoate reduction in liver: Possible role of cytochrome P-450 in liver microsomes.Mol. Pharmacol. 4:541–548 (1968).
A. H. Anton. The relation between the binding of sulfonamides to albumin and their antibacterial efficacy.J. Pharmacol. Exp. Ther. 129:282–290 (1960).
J. A. F. de Silva and I. Bekersky. Determination of clonazepam and flunitrazepam in blood by electron-capture gas-liquid chromatography.J. Chromatog. 99:447–460 (1974).
O. M. Bakke, M. Bending, J. Aarbakke, and D. S. Davies.C-Antipyrine as a model compound in the study of drug oxidation and enzyme induction in individual surviving rats.Acta Pharmacol. Toxicol. 35:91–97 (1974).
C. M. Metzler, G. L. Elfring, and A. J. McEwen.A User's Manual for NONLIN and Associated Programs, Upjohn Co., Kalamazoo, Mich., April 20, 1974.
H. G. Boxenbaum, S. Riegelman, and R. M. Elashoff. Statistical estimations in pharmacokinetics.J. Pharmacokin. Biopharm. 2:123–148 (1974).
R. L. Williams, T. F. Blaschke, P. J. Meffin, K. L. Melmon, and M. Rowland. Influence of viral hepatitis on the disposition of two compounds with high hepatic clearance: Lidocaine and indocyanine green.Clin. Pharmacol. Ther. 20:290–299 (1976).
R. A. Branch, D. G. Shand, G. R. Wilkinson, and A. S. Nies. Increased clearance of antipyrine andd-propranolol after phenobarbital treatment in the monkey: Relative contributions of enzyme induction and increased hepatic blood flow.J. Clin. Invest. 53:1101–1107 (1974).
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Bekersky, I., Maggio, A.C., Mattaliano, V. et al. Influence of phenobarbital on the disposition of clonazepam and antipyrine in the dog. Journal of Pharmacokinetics and Biopharmaceutics 5, 507–512 (1977). https://doi.org/10.1007/BF01061731
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DOI: https://doi.org/10.1007/BF01061731