Summary
The pharmacokinetics and distribution in brain and cerebellum of diazepam after a single dose were studied in middle aged (6 months) and old (18 months) rats. Following the single intravenous bolus of 5 mg/kg diazepam was eliminated more slowly in old rats (T 1/2(β)=3.1h) than in middle aged rats (1.4 h). This was due to an increase in the apparent volume of distribution Vdβ from 11.0 l/kg (control rats) to 29.5l/kg. Concentrations of diazepam in brain and cerebellum were in the same range (0.5–1.1 ng/mg) in both groups after this dose. We conclude that the distribution of diazepam is age-dependent which might be due to an altered body composition.
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References
Bender, A. D.: Pharmacologic aspects of aging: a survey of the effects of increasing age on drug activity in adults. J. Am. Geriatr. Soc. 12, 114–134 (1964)
Berman, M., Weiss, M. F.: SAAM manual, Laboratory of theoretical biology. National Institutes of Health, Bethesda, MD (1974)
Boston Collaborative Surveillance Program: Clinical depression on the central nervous system due to diazepam and chlordiazepoxide in relation to cigarette smoking and age. N. Engl. Med. 288, 277–280 (1973)
Costa, E., Guidotti, A., Mao, C. C., Suria, A.: New concepts on the mechanism of action of benzodiazepines. Life Sci. 17, 167–186 (1975)
Gal, P., Jusko, W. J., Yurchak, A. M., Franklin, B. A.: Theophylline disposition in obesity. Clin. Pharmacol. Ther. 23, 438–444 (1978)
Gibaldi, M., Nagashima, R., Levy, G.: Relationship between drug concentration in plasma or serum and amount of drug in the body. J. Pharm. Sci. 58, 193–197 (1969)
Jusko, W. J.: Factors affecting the pharmacokinetics of some psychoactive drugs. In: Clinical pharmacology of psychoactive drugs; Alcoholism and Drug Addiction Research Foundation Toronto, (E. Sellers ed.): pp. 55–72 (1975)
Jusko, W. J., Gibaldi, M.: Effects of change in elimination on various parameters of the two-compartment open model. J. Pharm. Sci. 61, 1270–1273 (1972)
Klotz, U., Wilkinson, G. R.: Hepatic elimination of drugs in the elderly. In: Liver and aging, K. Kitani (Ed.), pp. 367–380. Elsevier North-Holland Biomedical Press 1978
Klotz, U., Avant, G. R., Hoyumpa, A., Schenker, S., Wilkinson, G. R.: The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J. Clin. Invest. 55, 347–359 (1975)
Mao, C. C., Guidotti, A., Costa, E.: Evidence for an involvement of GABA in the mediation of the cerebellar cGMP decrease and the anticonvulsant action if diazepam. Naunyn-Schmiedeberg's Arch. Pharmacol. 289, 369–378 (1975)
Möhler, H., Okada, T.: Benzodiazepine receptor: Demonstration in the central nervous system. Science 198, 849–851 (1977)
Riegelman, S., Loo, J. C. K., Rowland, M.: Shortcomings in pharmacokinetic analysis by conceiving the body to exhibit the properties of a single compartment. J. Pharm Sci. 57, 117–123 (1968)
Squires, R. F., Breastrup, C.: Benzodiazepine receptors in rat brain. Nature 266, 732–734 (1977)
Westlake, W. J.: Time integral of drug concentration in the central (plasma) compartment. J. Pharm. Sci. 59, 722–723 (1970)
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Klotz, U. Effect of age on levels of diazepam in plasma and brain of rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 307, 167–169 (1979). https://doi.org/10.1007/BF00498459
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DOI: https://doi.org/10.1007/BF00498459