Diazoxide is given by rapid intravenous injection for the urgent reduction of high blood pressure in patients with all grades of renal function. Oral diazoxide produces less consistent effects. Protein binding of diazoxide is reduced in renal failure and this can be related to reduction of albumin concentration. There is a relation between impairment of renal function and the hypotensive effect of rapidly injected diazoxide. This is explicable in terms of the greater concentration of free (unbound) drug achieved after rapid injection in patients with renal failure. Renal clearance of diazoxide and its metabolites is impaired in renal failure but this is unlikely to affect its activity.
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Calesnick, B.; Katchen, B. and Black, J.: Importance of dissolution rates in producing effective diazoxide blood levels in man. Journal of Pharmaceutical Sciences 54: 1277–1280 (1965).
Charles, M.A. and Darnforth, E.: Nonketoacidotic hyper-glycaemia and coma during intravenous therapy in uraemia. Diabetes 20: 501–503 (1971).
Crout, J.R.; Andreasen, F.V.V.; Parks, R.I. and Heimbach, D.M.: Intravenous diazoxide in hypertension. Clinical Research 18: 337 (1970).
Dayton, P.G.; Pruitt, A.W.; Faraj, B.A. and Israili, Z.H.: Metabolism and disposition of diazoxide. Drug Metabolism and Disposition 3: 226–229 (1975).
Finnerty, F.A.; Kakaviatos, N.; Tuckman, J. and Magill, J.: Clinical evaluation of diazoxide, a new treatment for hypertension. Circulation 28: 203–208 (1963).
Hamby, W.M.; Jankowski, G.J.; Pouget, J.; Dunea, G. and Gantt, C.L.: Intravenous use of diazoxide in treatment of severe hypertension. Circulation 37: 169–174 (1968).
Harrison, B.D.; Putter, T.W. and Taylor, R.T.: Severe non-ketotic hyperglycaemic precoma in a hypertensive patient. Lancet 2: 599–600 (1972).
Heinrich, W.L.; Cronin, R. Miller, P.O. and Anderson, R.J.: Hypotensive sequelae of diazoxide and hydrallazine therapy. Journal of the American Medical Association 237: 264 (1977).
Johnson, B.F.: Diazoxide and renal function in man. Clinical Pharmacology and Therapeutics 12: 815–824 (1971).
Johnson, B.F. and Kapur, M.: The influence of rate of injection upon the effects of diazoxide. American Journal of Medical Science 263: 481–488 (1972).
O’Malley, K.; Velasco, M.; Pruitt, A. and McNay, J.L.: Decreased plasma protein binding in uraemia. Clinical Pharmacology and Therapeutics 18: 53–58 (1975).
Mroczek, W.M.; Leibel, B.A.; Davidov, M. and Finnerty, F.A.: The importance of rapid administration of diazoxide in accelerated hypertension. New England Journal of Medicine 285: 603–606 (1971).
Mussche, M.M.; De Broe, M.E. and Belpaire, F.M.: Oral diazoxide contraindicated in severe hypertension with renal failure. Clinical Nephrology 4: 99–103 (1975).
Mathew, T.H. and Kincaid-Smith, P.: The use of diazoxide in hypertensive crises with special reference to the control of hypertension in severe renal failure. Drugs 2: 73–77 (1971).
Odar-Cederlof, J.; Lunde, P. and Sjoqvist, F.: Abnormal pharmacokinetics of Phenytoin in a patient with uraemia. Lancet 2: 831–832 (1970).
Pearson, R.M. and Breckenridge, A.M.: Renal function, protein binding and the pharmacological response to diazoxide. British Journal of Clinical Pharmacology 3: 169–175 (1976).
Pohl, J.E.F. and Thurston, H.: Use of diazoxide in hypertension with renal failure. British Medical Journal 4: 142–145 (1971).
Pruitt, A.W. and Dayton, P.G.: A comparison of binding of drugs to adult and cord plasma. European Journal of Clinical Pharmacology 4: 59–62 (1971).
Pruitt, A.W.; Dayton, P.G. and Patterson, J.H.: Disposition of diazoxide in children. Clinical Pharmacology and Therapeutics 14: 73–82 (1973).
Pruitt, A.W.; Faraj, B.A. and Dayton, P.G.: Metabolism of diazoxide in man and experimental animals. Journal of Pharmacology and Experimental Therapeutics 188: 248–256 (1974).
Reidenberg, M.M.; Odar-Cederlof, J.; von Bahr, C.; Borga, O. and Sjoqvist, F.: Protein binding of diphenylhydantoin and desmethylimipramine in plasma from patients with poor renal function. New England Journal of Medicine 235: 264–266 (1971).
Review: Diazoxide. A review of its pharmacological properties and therapeutic use in hypertensive crises. Drugs 2: 78–137 (1971).
Richards, R.K.; Taylor, J.D. and Keuter, K.E.: Effect of nephrectomy on the duration of sleep following administration of thiopental and hexobarbital. Journal of Pharmacology and Experimental Therapeutics 108: 461–473 (1953).
Sadee, W.; Segal, J. and Finn, C.: Diazoxide urine and plasma levels in humans by stable-isotope dilution mass fragmento-graphy. Journal of Pharmacokinetics and Biopharmaceutics 1: 295–305 (1973).
Sellers. E.M. and Koch-Weser, J.: Protein binding and vascular activity of diazoxide. New England Journal of Medicine 281: 1141–1145 (1969).
Sellers. E.M. and Koch-Weser, J.: Influence of intravenous injection rate on protein binding and vascular activity of diazoxide. Annals of the New York Academy of Sciences 226: 319–332 (1973).
Sellers, E.M. and Koch-Weser, J.: Binding of-diazoxide and other benzothiadiazines to human albumin. Biochemical Pharmacology 23: 553–556 (1974).
Sjoholm, I.; Kober, A.; Odar-Cederlof, I. and Borga, O.: Protein binding of drugs in uraemic and normal serum. The role of endogenous binding inhibitors. Biochemical Pharmacology 25: 1205–1213 (1976).
Sloane, R.A.: Administration of diazoxide. British Medical Journal 2: 1259 (1976).
Symchowicz, S.; Winston. L.; Black, J.; Smith. M.; Calesnick, B. and Tabachnick, I.I.A.: Diazoxide blood levels in man. Journal of Pharmaceutical Science 56: 912–914 (1967).
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Pearson, R.M. Pharmacokinetics and Response to Diazoxide in Renal Failure. Clin Pharmacokinet 2, 198–204 (1977). https://doi.org/10.2165/00003088-197702030-00004