The Effect of Cyclosporine on the Pharmacokinetics of Prednisolone in Renal

Rocci, Mario L.; Tietze, Karen J.; Lee, Jean; Harris, Harriet A.; Danzeisen, Janice; Burke, James F.

doi:10.1097/00007890-198803000-00032

Cited by 23 publications

(8 citation statements)

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“…The effect of diltiazem on prednisone metabolism in patients taking CsA may be more difficult to assess, as diltiazem will alter CsA metabolism, and CsA itself may ( 22) or may not ( 23) have an effect on prednisone metabolism. However, it appears reasonable to suggest that the enhancement of prednisolone exposure by diltiazem after an oral dose of prednisone may contribute to chronic immunosuppression in some patients and worsen other side‐effects, which may be of particular importance in pediatric patients.…”

Section: Discussionmentioning

confidence: 99%

Diltiazem retards the metabolism of oral prednisone with effects on T‐cell markers

Imani

Jusko

Steiner

1999

Pediatric Transplantation

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The area under the time-plasma concentration curve (AUC) was measured for prednisolone (the major active metabolite of prednisone) after ingestion of 15 mg of prednisone (phase 1) and again after 3 d of oral diltiazem (180 mg/d) followed by the same dose of oral prednisone (phase 2) in eight normal adult patients. Diltiazem increased the prednisolone AUC by 21% (range 3-38%), from 1297 +/- 157 ng/h/mL to 1560 +/- 169 ng/h/mL (p = 0.001). This effect was associated with a greater decrease from baseline in CD3+ lymphocyte number at 4 h after prednisone ingestion (596 +/- 175 vs. 516 +/- 140, p = 0.05), a larger percentage decrease of circulating CD3+ lymphocytes at 8 h (43 +/- 19% vs. 53 +/- 19%, p = 0.04), and a decrease in the number of CD3+ CD8+ T cells at 4 h post-prednisone ingestion (279 +/- 81 vs. 236 +/- 51, p = 0.04). Diltiazem retards prednisolone metabolism and when used chronically with prednisone could conceivably, in some patients, enhance its immunologic and other clinical effects. Potentiation of prednisone side-effects by diltiazem may be of special interest in pediatric patients, and possible diltiazem-prednisone interactions merit study in this population.

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Section: Discussionmentioning

confidence: 99%

Diltiazem retards the metabolism of oral prednisone with effects on T‐cell markers

Imani

Jusko

Steiner

1999

Pediatric Transplantation

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“…The plasma protein binding of prednisolone in liver transplant patients has been reported to be lower than in normal subjects (Townsend et al 1983). No changes in the transcortin or albumin concentration or albumin-prednisolone affinity constant were observed after transplantation (Rocci et al 1988). The binding characteristics of prednisolone immediately following transplantation have not been evaluated.…”

Section: Distributionmentioning

confidence: 99%

Clinical Pharmacokinetics in Organ Transplant Patients

Venkataramanan

Habucky

Burckart

et al. 1989

Clinical Pharmacokinetics

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Diseases of the liver, kidney and heart influence the pharmacokinetics of several drugs. Organ transplantation is an accepted therapeutic option for the treatment of several disease states associated with these organs. Recently, there has been an increase in both graft and patient survival after transplantation of the liver, heart, kidney and bone marrow. Such patients normally receive a wide range of drugs, and optimisation of drug therapy requires a thorough understanding of the pharmacokinetics and pharmacodynamics of these drugs in transplant patients. However, only limited studies have been carried out to characterise drug kinetics in these situations. Available information indicates that drug kinetics cannot be considered normal in transplant patients. Drug absorption generally appears to be similar to that in healthy subjects. The plasma protein binding of drugs that primarily bind to albumin increases after transplantation, but remains lower than that observed in healthy subjects. While the binding of certain basic drugs may increase after transplantation due to an increase in the concentration of alpha 1-acid glycoprotein, a lower albumin concentration may mask this effect. Oxidative and conjugative metabolism as measured by the kinetics of antipyrine (phenazone) and paracetamol (acetaminophen) is normal, while the metabolism of steroids may be impaired. Serum creatinine does not appear to be a good indicator of the functional status of the kidney in transplant patients. It is also important to realise that there will be time-dependent changes in several kinetic parameters of drugs due to improvement in the physiological function from that associated with the disease state to that of the normal state. Individualisation and close monitoring of drug therapy is necessary in transplant patients.

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“…In a number of studies cyclosporine has been reported to decrease the clearance of prednisolone by 25% to 30% . However, 3 smaller studies did not find an interaction between cyclosporine and prednisone and suggested that the drug interaction may depend on dosage, route of administration, disease course, or other factors . Given that CYP3A accounts for only 18% of steroid metabolism, and this subject's PK parameters were all within the range of the other subjects, her PK was included in our analysis.…”

Section: Methodsmentioning

confidence: 85%

Prednisone Pharmacokinetics During Pregnancy and Lactation

Ryu

Easterling

Caritis

et al. 2018

The Journal of Clinical Pharma

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To evaluate the steady-state pharmacokinetics of prednisone and its metabolite prednisolone in pregnant and lactating female subjects, 19 subjects received prednisone (4-40 mg/day orally) in early (n = 3), mid (n = 9), and late (n = 13) pregnancy as well as postpartum with (n = 2) and without (n = 5) lactation. Serial blood and urine samples were collected over 1 dosing interval. Prednisone and its metabolite, prednisolone, steady-state noncompartmental pharmacokinetic parameters were estimated. During pregnancy, prednisone apparent oral clearance increased with dose (35.1 ± 11.4 L/h with 5 mg, 52.6 ± 5.2 L/h with 10 mg, and 64.3 ± 6.9 L/h with 20 mg, P = .001). Similarly, unbound prednisone apparent oral clearance increased with dose. In addition, prednisolone renal clearance increased with dose (0.3 ± 0.3 L/h with 5 mg, 0.5 ± 0.4 L/h with 10 mg, and 1.3 ± 1.1 L/h with 20 mg, P = .002). Higher prednisone (r = 0.57, P ≤ .05) and prednisolone (r = 0.75, P ≤ .05) concentrations led to a higher percentage of unbound drug. Breast-milk/plasma area under the concentration-time curve ratios were 0.5-0.6 for prednisone and 0.02-0.03 for prednisolone. Relative infant doses were 0.35% to 0.53% and 0.09% to 0.18%, for prednisone and prednisolone, respectively. Prednisone and prednisolone exhibit dose- and concentration-dependent pharmacokinetics during pregnancy, and infant exposure to these agents via breast milk is minimal.

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The Effect of Cyclosporine on the Pharmacokinetics of Prednisolone in Renal

Cited by 23 publications

References 0 publications

Diltiazem retards the metabolism of oral prednisone with effects on T‐cell markers

Diltiazem retards the metabolism of oral prednisone with effects on T‐cell markers

Clinical Pharmacokinetics in Organ Transplant Patients

Prednisone Pharmacokinetics During Pregnancy and Lactation

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