+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Effect of heparin or salicylate infusion on serum protein binding and concentrations of phenytoin in serum brain and cerebro spinal fluid of rats



Effect of heparin or salicylate infusion on serum protein binding and concentrations of phenytoin in serum brain and cerebro spinal fluid of rats



Journal of Pharmacology & Experimental Therapeutics 219(1): 42-48



Whether administration of heparin caused displacement of an acidic drug from serum protein binding sites in vitro as suggested by several groups of investigators was studied. Rats were injected and infused with phenytoin to produce steady-state serum concentrations of .apprx. 25 .mu.g/ml. After 2 h, some animals also received injections and infusions of heparin or salicylic acid. Salicylic acid (.alpha. 300 .mu.g/ml), a classical inhibitor of phenytoin protein binding, reduced the steady-state serum concentration of total (free plus bound) phenytoin but had no significant effect on the steady-state serum concentration of free phenytoin or on the concentrations of phenytoin in CSF and brain. The concentrations of phenytoin in CSF were almost identical to the free phenytoin concentrations in serum. Similar effects were observed with respect to 5-(p-hydroxyphenyl)-5-phenylhydantoin and were due to displacement of this major metabolite of phenytoin from serum protein binding sites by salicylate. Heparin administration caused an apparent increase of the steady-state plasma concentration of free phenytoin when determined as the product of the concentration of total phenytoin and the free fraction measured by in vitro equilibrium dialysis. Since heparin treatment had no significant effect on the total concentrations of phenytoin in plasma, CSF and brain, the apparent displacement of phenytoin from plasma proteins occurred in vitro, after collection of blood samples from heparinized animals.

Please choose payment method:






(PDF emailed within 1 workday: $29.90)

Accession: 005243480

Download citation: RISBibTeXText

PMID: 7288614


Related references

Kinetics of drug action in disease states 1. effect of infusion rate on pheno barbital concentrations in serum brain and cerebro spinal fluid of normal rats at onset of loss of righting reflex. Journal of Pharmacology and Experimental Therapeutics 229(1): 44-50, 1984

The cerebro spinal fluid serum and saliva serum ratio of phenytoin in epileptic patients with and without impairment of the blood cerebro spinal fluid barrier. Wada, J A And J K Penry (Ed ) Advances in Epileptology, Vol 10 Epilepsy International Symposium, Vancouver, B C , Canada, 1978 Xxxiii+523p Raven Press: New York, N Y , Usa Illus Maps P486, 1980

Phenytoin and pheno barbital concentrations in cerebro spinal fluid influence of blood brain cerebro spinal fluid barrier. Epilepsia 22(2): 236-237, 1981

Cerebro spinal fluid concentrations and serum protein binding of diazepam and n demethyl diazepam. Acta Pharmacologica Et Toxicologica Supplementum: 35, 1974

The concentration of sodium potassium calcium magnesium and chloride in the cerebro spinal fluid and the relation between the concentrations of these elements in cerebro spinal fluid and serum. Zeitschrift fuer Klinische Chemie und Klinische Biochemie 10(10): 462-466, 1972

Protein concentration of cerebro spinal fluid and serum cerebro spinal fluid ratio of glucose and electrolytes in infants and children. Helvetica Paediatrica Acta 36(3): 217-228, 1981

Cerebro spinal fluid vs. serum concentrations of 5 fluoro uracil allopurinol and oxypurinol during treatment of metastatic brain cancer with 5 fluoro uracil infusion allopurinol and radiation. Cancer Treatment Reports 66(3): 571-574, 1982

Cerebro spinal fluid serum ratios of primidone inferences to protein binding. Epilepsia 18(2): 291, 1977

Binding of iodine 125 myelin basic protein by serum and cerebro spinal fluid. Clinical & Experimental Immunology 11(4): 595-603, 1972

Observations of blood cerebro spinal fluid and cerebro spinal fluid blood barrier using radio iodinated serum albumin iodine 131 in acute focal brain hypoxia. Purkyne, J E (Edited By) Iii Symposium Neurologicum Danubianum Internationale (Lectionum Excerpta) 156p Illus Neurological Society Of The Czechoslovak Medical Association: Bratislava, Czechoslovakia 123-124, 1970

Brain serum and cerebro spinal fluid serum ratios after a single dose of di propyl acetic acid. Electroencephalography & Clinical Neurophysiology 43(4): 509-510, 1977

Kinetics of drug action in disease states. XIV. Effect of infusion rate on pentylenetetrazol concentrations in serum, brain and cerebrospinal fluid of rats at onset of convulsions. Journal of Pharmacology and Experimental Therapeutics 234(3): 624-628, 1985

Relationships among dose serum and cerebro spinal fluid levels and urinary output in pheno barbital and phenytoin treatment of epileptics. Revue Roumaine de Medecine Neurologie et Psychiatrie 13(2): 101-110, 1975

Chronological development of the permeability of the blood cerebro spinal fluid barrier as evaluated from the serum cerebro spinal fluid concentration ratio of proteins. Nichidai Igaku Zasshi 39(4): 365-372, 1980

Significance of quantitative determination of immuno globulin and albumin in cerebro spinal fluid and serum for evaluation to positive syphilis tests in cerebro spinal fluid. Zentralblatt fuer Bakteriologie Parasitenkunde Infektionskrankheiten und Hygiene Erste Abteilung Originale Reihe A Medizinische Mikrobiologie und Parasitologie 243(4): 439-440, 1979