Displacement of thiopental from human serum albumin by associated drugs.

Displacement of thiopental from its binding sites to 4% human serum albumin solution was studied in vitro. Experimental conditions were selected to reproduce a physiological situation. Associations were studied according to the therapeutic conditions of use of the substances (drug and protein concentrations). The unbound fraction of thiopental was obtained by equilibrium dialysis at 37 degrees C and pH 7.4. Eleven drugs were associated with thiopental in 50 combinations of drugs and molar ratios. Bromhexine, citocoline, dextromoramide, dexamethasone, and methotrimeprazine had no effect on thiopental binding. The unbound fraction of thiopental significantly increased with cefamandole, cefazolin, diazepam, desmethyldiazepam, furosemide, and fentanyl. At usual therapeutic drug concentrations, the unbound fraction increase was < 5%. Higher values, however still < 10%, were found with associated drugs that were added at maximal concentrations observed in therapy. The displacement of thiopental from its albumin binding by drugs that are normally associated with the treatment of intracranial hypertension does not modify the pharmacokinetic parameters or pharmacological effect of thiopental.

[1]  D. Morgan,et al.  Pharmacokinetics and plasma binding of thiopental. II: Studies at cesarean section. , 1981, Anesthesiology.

[2]  J. Granry,et al.  Thiopental Pharmacokinetics under Conditions of Long‐term Infusion , 1985, Anesthesiology.

[3]  A. Brown,et al.  Status epilepticus treated by intravenous infusions of thiopentone sodium. , 1967, British medical journal.

[4]  S. Csögör,et al.  Enhancement of thiopentone anaesthesia by sulphafurazole. , 1970, British journal of anaesthesia.

[5]  A. Hume,et al.  Ultra‐short‐acting barbiturates as oral hypnotic agents in man , 1966, Clinical pharmacology and therapeutics.

[6]  S. Kaukinen,et al.  Prolongation of thiopentone anaesthesia by probenecid. , 1980, British journal of anaesthesia.

[7]  F. Andreasen,et al.  Thiopentone sensitivity in young and elderly women. , 1983, British journal of anaesthesia.

[8]  D. Perrier,et al.  Thiopental disposition as a function of age in female patients undergoing surgery. , 1982 .

[9]  P. G. Burch,et al.  Decreased protein binding and thiopental kinetics , 1982, Clinical pharmacology and therapeutics.

[10]  T. Langfitt,et al.  Resuscitation from coma due to head injury , 1978, Critical care medicine.

[11]  M. Ghoneim,et al.  Plasma protein binding of thiopental in patients with impaired renal or hepatic function. , 1975, Anesthesiology.

[12]  D. Morgan,et al.  Plasma binding of thiopentone in late pregnancy. , 1983, British journal of clinical pharmacology.

[13]  T. Haley,et al.  Pharmacological comparison of R(+), S(-) and racemic thiopentone in mice. , 1976, European journal of pharmacology.

[14]  J. Paull,et al.  Pharmacokinetics and plasma binding of thiopental. I: Studies in surgical patients. , 1981, Anesthesiology.

[15]  M. Ghoneim,et al.  Binding of Thiopental to Plasma Proteins: Effects on Distribution in the Brain and Heart , 1976, Anesthesiology.

[16]  G. Heinemeyer.  Clinical Pharmacokinetic Considerations in the Treatment of Increased Intracranial Pressure , 1987, Clinical pharmacokinetics.

[17]  B. Brodie,et al.  THE IMPORTANCE OF DISSOCIATION CONSTANT AND LIPID-SOLUBILITY IN INFLUENCING THE PASSAGE OF DRUGS INTO THE CEREBROSPINAL FLUID , 1960 .

[18]  L. C. Mark,et al.  Thiopental Metabolism by Human Liver in vivo and in vtro , 1965, Nature.

[19]  D. Perrier,et al.  Pharmacokinetic Properties of Thiopental in Two Patients Treated for Uncontrollable Seizures , 1979, Epilepsia.

[20]  J. Stoddart,et al.  Plasma and cerebrospinal fluid barbiturate levels during prolonged continuous thiopentone infusion , 1982, Anaesthesia.

[21]  Y. Sawada,et al.  Effect of sulfadimethoxine on thiopental distribution and elimination in rats. , 1981, Journal of pharmaceutical sciences.

[22]  D. Perrier,et al.  The "ultra-free" ultrafiltration technique compared with equilibrium dialysis for determination of unbound thiopental concentrations in serum. , 1981, Clinical chemistry.

[23]  M. Partinen,et al.  Status epilepticus treated by barbiturate anaesthesia with continuous monitoring of cerebral function. , 1981, British medical journal.

[24]  U. Wollert,et al.  Characterization of the binding of benzodiazepines to human serum albumin , 2004, Naunyn-Schmiedeberg's Archives of Pharmacology.

[25]  M. Farinotti,et al.  Thiopental Pharmacokinetics in Patients with Cirrhosis , 1983, Anesthesiology.

[26]  H. Michels,et al.  Differences in the binding of drugs to plasma proteins from newborn and adult man. II , 1977, European Journal of Clinical Pharmacology.

[27]  D. Stanski,et al.  Pharmacokinetics of high-dose thiopental used in cerebral resuscitation. , 1980, Anesthesiology.

[28]  L. C. Mark,et al.  The relationship between binding of thiopental to plasma and its distribution into adipose tissue in man, as measured by a spectrophotofluorometric method. , 1967, Biochemical pharmacology.

[29]  J. Michenfelder,et al.  Cerebral Protection by Thiopental during Hypoxia , 1973, Anesthesiology.

[30]  P. G. Burch,et al.  The Role of Metabolism and Protein Binding in Thiopental Anesthesia , 1983, Anesthesiology.

[31]  R. K. Richards,et al.  Pharmacokinetics and anesthetic potency of a thiopental isomer. , 1983, Journal of pharmaceutical sciences.