Biomedical subjects
D C Buss
Publications and source records attributed to D C Buss.
The ex vivo plasma protein binding of theophylline in renal disease.
The plasma protein binding of theophylline was measured in 21 patients with renal disease and 21 healthy age and sex matched controls. The percentage of theophylline unbound to plasma was greater in patients with nephrotic syndrome and in chronic renal failure than in controls. In nephrotic syndrome the impairment of drug binding mirrored the marked degree of hypoalbuminaemia seen in this condition but in chronic renal failure the impairment of protein binding was greater than would be expected from the plasma albumin concentration changes. The percentage of theophylline free in plasma in renal disease may be increased (by as much as 50%). Such changes should be taken into account in interpreting the relationship between total plasma theophylline concentration and drug effect in renal disease.
Amiodarone reduces plasma warfarin clearance in man.
Amiodarone is an effective antiarrhythmic agent whose use is associated with several drug interactions one of which is potentiation of the action of warfarin. The mechanism of this interaction has hitherto been unclear. We examined possible mechanisms in eight patients. Total plasma warfarin clearance was found to be reduced by amiodarone. No change was detected in the binding of warfarin to plasma proteins. No relationship was found between plasma amiodarone concentrations and the change in warfarin clearance.
Amiodarone does not affect digoxin kinetics in the rabbit.
It has been reported that amiodarone may interact with digoxin in man. We investigated the effects of amiodarone pretreatment (35 mg kg-1 day-1) on the pharmacokinetics of a single dose of digoxin (50 micrograms kg-1) in 6 rabbits. Total body clearance of digoxin was 138.84 +/- 44.67 and 147.99 +/- 29.17 ml min-1, serum half life 187.9 +/- 60.9 and 181.34 +/- 25.57 min and volume of distribution 35.4 +/- 8.54 and 37.8 +/- 3.9 litres before and after amiodarone treatment, respectively. None of these changes were statistically significant. We conclude that the presence of an amiodarone-induced change in digoxin pharmacokinetics in the rabbit was not evident and that other animal models will be necessary for studying this interaction.
Should we routinely measure free plasma phenytoin concentration?
The plasma protein binding of phenytoin was investigated in 56 epileptic patients attending the outpatient clinic. The free phenytoin fraction was measured by equilibrium dialysis at 37 degrees C and the total concentration by a homogenous enzyme immunoassay technique. The free fraction ranged from 0.123 to 0.177 (median 0.144, mean +/- s.d. = 0.145 +/- 0.12). Distribution was consistent with normality. Four of the patients were also taking sodium valproate. The median free fraction of phenytoin in these patients was 0.174, 21% higher than that of the total group (P less than 0.05). The total concentration of phenytoin varied from 0.3 to 29.4 micrograms/ml (median 12 micrograms/ml, mean +/- s.d. = 13.31 +/- 6.13 micrograms/ml) and the free fraction was not related to the total drug concentration. There was a highly significant relationship between free phenytoin concentration and total phenytoin concentration (r = 0.986, P less than 0.001). There appears to be very little variability in protein binding of phenytoin in epileptic patients and thus total plasma phenytoin concentration closely reflects the free (unbound) drug concentration. Routine estimation of free plasma phenytoin concentration is therefore unnecessary and should be reserved for those patients where alteration in binding is likely, e.g. renal or hepatic disease or where adverse effects occur at unexpectedly low total phenytoin concentrations.