Effect of heparin administration on plasma binding of benzodiazepines.

Desmond, PV; Roberts, RK; Wood, A. J. J.; Dunn, GD; Wilkinson, G. R.; Schenker, Steven

doi:10.1111/j.1365-2125.1980.tb05829.x

Cited by 59 publications

(12 citation statements)

References 12 publications

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“…Heparin causes a release of the enzymes lipoprotein lipase and hepatic lipase, which in turn hydrolyse plasma triglycerides into non-esterified fatty acids (NEFA) [Fielding et aI., 1974;Krauss et ai., 1974;LaRosa et al, 1972]. Non-esterified fatty acids have been shown to competitively inhibit drug binding to plasma proteins (Desmond et al, 1980;Kessler et al, 1979;Routledge et ai., 1979;Storstein and Janssen, 1976;Van der Vijgh and Oe, 1977;Wood et ai., 1979b). Wood et ai.…”

Section: Administration Of Heparinmentioning

confidence: 96%

Effect of Cardiopulmonary Bypass on the Pharmacokinetics of Drugs

Holley

Ponganis

Stanski

1982

Clinical Pharmacokinetics

124

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The cardiopulmonary bypass apparatus must temporarily substitute for the cardiac and pulmonary function of the patient undergoing heart surgery. In order to meet the metabolic needs of the patient and the technical demands of the surgeon, within the limits of engineering technology, a number of major alterations are made in normal physiology. The patient is typically cooled to 27 degrees C and perfused with a non-pulsatile flow of blood which has been diluted with saline to a haematocrit in the mid-20s. Blood flow and pressure are often considerably less than normal. Blood coagulation is prevented by administration of a massive dose of heparin. Central redistribution of blood flow, elaboration of stress-reactant hormones, and fluid and electrolyte shifts occur in response to these changes. In the postoperative period, these alterations are reversed, and normal physiology is restored. Effects upon the pharmacokinetics of drugs are anticipated. The clearance of many drugs may be reduced. Protein binding is diminished by haemodilution, but may rise above normal in the postoperative period for basic drugs which bind to alpha 1-acid glycoprotein. Changes in volume of distribution depend upon the opposing influences of protein binding and reduced peripheral perfusion. Previous studies on the pharmacokinetics of drugs during and after cardiopulmonary bypass illustrate many of these effects. The clearance of digoxin, fentanyl, and the cephalosporins is reduced after cardiopulmonary bypass, and the volume of distribution of cefazolin is increased during cardiopulmonary bypass. Studies of digitoxin and propranolol are also reviewed. Many of the investigations in this area of study have been limited by logistical and methodological factors. Thus, the effects of cardiopulmonary bypass on the pharmacokinetics of drugs are incompletely understood, and the subject merits further attention.

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Section: Administration Of Heparinmentioning

confidence: 96%

Effect of Cardiopulmonary Bypass on the Pharmacokinetics of Drugs

Holley

Ponganis

Stanski

1982

Clinical Pharmacokinetics

124

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“…Pharmacokinetic parameters were estimated in each patient by simultaneous fi tting of the observed data in the three phases to Eqs. (1), (17), and (18) using the nonlinear least-squares regression program MULTI. 8 …”

Section: Appendix 1 Appendixmentioning

confidence: 99%

Pharmacokinetic analysis of flomoxef in children undergoing cardiopulmonary bypass and modified ultrafiltration

Masuda

Kurosaki

Ishino

et al. 2008

Gen Thorac Cardiovasc Surg

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“…A heparin (Pularin, Duncan Flockhart) saline solution (2 units/ml) was used at each sampling time to flush the butterfly needle; no more than 5 ml was used on each occasion. This concentration of heparin is well below that known to influence diazepam binding to serum proteins (Desmond et al, 1980;Naranjo et al, 1980). Blood samples were taken before the injection and 2, 5, 10, 20, 30, 60, 90, 120 inin and 4, 8, 12, 24, 28, 32, 48, 56, 72, 80, and 96 h after drug administration.…”

Section: Methodsmentioning

confidence: 99%

Valproic acid and diazepam interaction in vivo.

Dhillon¹,

Richens²

1982

Brit J Clinical Pharma

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I The effect of oral administration of sodium valproate (1500 mg daily) on the distribution and elimination kinetics of intravenously administered diazepam in six healthy volunteers has been studied. 2 During valproate administration the unbound fraction of diazepam in serum increased approximately two fold. This was accompanied by a significant increase in apparent volume of distribution and plasma clearance of diazepam. 3 There was a positive correlation between the change in free fraction and the increase in both apparent volume of distribution and plasma clearance of the drug. 4 The concentration of unbound diazepam in serum (calculated from the percent free diazepam and total serum concentration) was significantly higher during valproate administration. Both the intrinsic clearance and volume of distribution of unbound drug were significantly reduced. 5 Mean serum N-desmethyldiazepam levels were significantly lower during valproate coadministration. 6 These results suggest that valproic acid displaces diazepam from plasma protein binding sites and inhibits its metabolism.

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Effect of heparin administration on plasma binding of benzodiazepines.

Cited by 59 publications

References 12 publications

Effect of Cardiopulmonary Bypass on the Pharmacokinetics of Drugs

Effect of Cardiopulmonary Bypass on the Pharmacokinetics of Drugs

Pharmacokinetic analysis of flomoxef in children undergoing cardiopulmonary bypass and modified ultrafiltration

Valproic acid and diazepam interaction in vivo.

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