Clinical pharmacokinetics of cardiac glycosides in patients with renal dysfunction.
The pharmacokinetics of different cardiac glycosides are altered by renal dysfunction in different ways, depending on their basic pharmacokinetic properties. Digoxin: The linearity of digoxin pharmacokinetics is unchanged by renal dysfunction, as is the bioavailability. Protein binding may be slight...
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| Format: | Journal article |
| Language: | English |
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1983
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| _version_ | 1797070465439629312 |
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| author | Aronson, J |
| author_facet | Aronson, J |
| author_sort | Aronson, J |
| collection | OXFORD |
| description | The pharmacokinetics of different cardiac glycosides are altered by renal dysfunction in different ways, depending on their basic pharmacokinetic properties. Digoxin: The linearity of digoxin pharmacokinetics is unchanged by renal dysfunction, as is the bioavailability. Protein binding may be slightly reduced, but the change is of no clinical significance. The apparent volume of distribution is reduced by one-third to one-half, the change being roughly proportional to the degree of renal impairment. The significance of this change in terms of adjustment of the loading dose is controversial. The renal clearance of digoxin is reduced in renal dysfunction and becomes very closely related to the measured creatinine clearance at values of creatinine clearance below 30 ml/min. Digitoxin: There are technical problems with the measurement of digitoxin because of the need to separate digitoxin and its metabolites chromatographically before using the measurement techniques commonly applied. Such separation has not always been carried out, and this makes the interpretation of the available data more difficult. The bioavailability of digitoxin is unaffected by renal dysfunction. Protein binding is probably significantly reduced but the clinical significance of this effect is unclear since the apparent volume of distribution and total body clearance of digitoxin appear to be unchanged. In the nephrotic syndrome, which must be considered separately from the other forms of renal dysfunction, there is impaired protein binding but also probably loss of protein bound drug via the renal glomerulus. This leads to a proportionately large increase in total body and renal clearances, a shortening of the half-life and a fall in the steady-state plasma digitoxin concentrations. In other forms of renal dysfunction there is probably no change in half-life or in steady-state plasma digitoxin concentrations. There does seem to be a decrease in digitoxin renal clearance but this may be compensated for by increases in non-renal clearance, both by non-renal excretion of unchanged digitoxin and by metabolic clearance, with increased formation of the active hydroxylated and hydrolysed metabolites, as well of the relatively inactive reduced metabolites. Overall, the changes seem to contribute little of clinical importance. Little digitoxin is removed from the body by dialysis procedures. Lanatoside C, deslanoside, and the acylated digoxins: Since these glycosides are largely metabolised to digotxin, one would expect changes in their pharmacokinetics similar to those of digoxin. However, there is only enough information to conclude that this is probably so in the case of β-methyldigoxin. The protein binding of β-methyldigoxin is reduced, as is its apparent volume of distribution, and total body clearance. The reduction in total body clearance is mostly attributable to a reduction in renal clearance, which falls in parallel with creatinine clearance, although always remaining lower than creatinine clearance. Non-renal clearance falls little or not at all. As a result of these changes the ovarall half-life of β-methyldigoxin is prolonged and the fractional daily loss at steady-state is decreased. Dosages of β-methyldigoxin therefore need to be reduced in renal dysfunction. Little-β-methyldigoxin is removed by haemodialysis. For α-acetyldigoxin, renal clearance is reduced in proportion to renal function, and the half-life is prolonged. Little is removed by haemodialysis. Other glycosides: Little information is available about other cardiac glycosides. What little information there is, however, suggests that, as one would expect, the half-life is prolonged and renal clearance reduced for those glycosides which are mostly eliminated via the urine, while little or no change occurs for those glycosides which are mostly metabolised. Thus, for ouabain (g-strophanthin), and k-strophanthin, the half-life is prolonged and renal excretion decreased, while for proscillaridin, methylproscillaridin, and peruvoside there is no change. None of these glycosides is much affected by haemodialysis. Despite the changes in pharmacokinetics of digoxin compared with digitoxin, there is little to choose between the two drugs for use in patients with renal dysfunction. Arguments in favour of one or other can be marshalled but there is no good evidence that one is preferable to the other. |
| first_indexed | 2024-03-06T22:39:14Z |
| format | Journal article |
| id | oxford-uuid:5af36b31-9517-4663-b5b8-65b7fee12eeb |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:39:14Z |
| publishDate | 1983 |
| record_format | dspace |
| spelling | oxford-uuid:5af36b31-9517-4663-b5b8-65b7fee12eeb2022-03-26T17:19:06ZClinical pharmacokinetics of cardiac glycosides in patients with renal dysfunction.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5af36b31-9517-4663-b5b8-65b7fee12eebEnglishSymplectic Elements at Oxford1983Aronson, JThe pharmacokinetics of different cardiac glycosides are altered by renal dysfunction in different ways, depending on their basic pharmacokinetic properties. Digoxin: The linearity of digoxin pharmacokinetics is unchanged by renal dysfunction, as is the bioavailability. Protein binding may be slightly reduced, but the change is of no clinical significance. The apparent volume of distribution is reduced by one-third to one-half, the change being roughly proportional to the degree of renal impairment. The significance of this change in terms of adjustment of the loading dose is controversial. The renal clearance of digoxin is reduced in renal dysfunction and becomes very closely related to the measured creatinine clearance at values of creatinine clearance below 30 ml/min. Digitoxin: There are technical problems with the measurement of digitoxin because of the need to separate digitoxin and its metabolites chromatographically before using the measurement techniques commonly applied. Such separation has not always been carried out, and this makes the interpretation of the available data more difficult. The bioavailability of digitoxin is unaffected by renal dysfunction. Protein binding is probably significantly reduced but the clinical significance of this effect is unclear since the apparent volume of distribution and total body clearance of digitoxin appear to be unchanged. In the nephrotic syndrome, which must be considered separately from the other forms of renal dysfunction, there is impaired protein binding but also probably loss of protein bound drug via the renal glomerulus. This leads to a proportionately large increase in total body and renal clearances, a shortening of the half-life and a fall in the steady-state plasma digitoxin concentrations. In other forms of renal dysfunction there is probably no change in half-life or in steady-state plasma digitoxin concentrations. There does seem to be a decrease in digitoxin renal clearance but this may be compensated for by increases in non-renal clearance, both by non-renal excretion of unchanged digitoxin and by metabolic clearance, with increased formation of the active hydroxylated and hydrolysed metabolites, as well of the relatively inactive reduced metabolites. Overall, the changes seem to contribute little of clinical importance. Little digitoxin is removed from the body by dialysis procedures. Lanatoside C, deslanoside, and the acylated digoxins: Since these glycosides are largely metabolised to digotxin, one would expect changes in their pharmacokinetics similar to those of digoxin. However, there is only enough information to conclude that this is probably so in the case of β-methyldigoxin. The protein binding of β-methyldigoxin is reduced, as is its apparent volume of distribution, and total body clearance. The reduction in total body clearance is mostly attributable to a reduction in renal clearance, which falls in parallel with creatinine clearance, although always remaining lower than creatinine clearance. Non-renal clearance falls little or not at all. As a result of these changes the ovarall half-life of β-methyldigoxin is prolonged and the fractional daily loss at steady-state is decreased. Dosages of β-methyldigoxin therefore need to be reduced in renal dysfunction. Little-β-methyldigoxin is removed by haemodialysis. For α-acetyldigoxin, renal clearance is reduced in proportion to renal function, and the half-life is prolonged. Little is removed by haemodialysis. Other glycosides: Little information is available about other cardiac glycosides. What little information there is, however, suggests that, as one would expect, the half-life is prolonged and renal clearance reduced for those glycosides which are mostly eliminated via the urine, while little or no change occurs for those glycosides which are mostly metabolised. Thus, for ouabain (g-strophanthin), and k-strophanthin, the half-life is prolonged and renal excretion decreased, while for proscillaridin, methylproscillaridin, and peruvoside there is no change. None of these glycosides is much affected by haemodialysis. Despite the changes in pharmacokinetics of digoxin compared with digitoxin, there is little to choose between the two drugs for use in patients with renal dysfunction. Arguments in favour of one or other can be marshalled but there is no good evidence that one is preferable to the other. |
| spellingShingle | Aronson, J Clinical pharmacokinetics of cardiac glycosides in patients with renal dysfunction. |
| title | Clinical pharmacokinetics of cardiac glycosides in patients with renal dysfunction. |
| title_full | Clinical pharmacokinetics of cardiac glycosides in patients with renal dysfunction. |
| title_fullStr | Clinical pharmacokinetics of cardiac glycosides in patients with renal dysfunction. |
| title_full_unstemmed | Clinical pharmacokinetics of cardiac glycosides in patients with renal dysfunction. |
| title_short | Clinical pharmacokinetics of cardiac glycosides in patients with renal dysfunction. |
| title_sort | clinical pharmacokinetics of cardiac glycosides in patients with renal dysfunction |
| work_keys_str_mv | AT aronsonj clinicalpharmacokineticsofcardiacglycosidesinpatientswithrenaldysfunction |