Pharmacokinetics of Sirolimus and Tacrolimus in Pediatric Transplant Patients

Schubert, Marika; Venkataramanan, Raman; Holt, David W.; Shaw, Leslie M.; McGhee, William; Reyes, Jorgé; Webber, Steve; Sindhi, Rakesh

doi:10.1111/j.1600-6143.2004.00411.x

Cited by 68 publications

(69 citation statements)

References 33 publications

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“…As pharmacokinetic data from children have shown a higher clearance rate than in adults [15,23] a dosage of 3 mg/m 2 /day in two doses was chosen and seems to result in reasonable drug exposure. However, therapeutic monitoring should be used to adjust sirolimus dosage, as the maintenance doses in our children with normal function of the transplanted liver differed between 0.8 and 5.4 mg/ m 2 /day.…”

Section: Discussionmentioning

confidence: 99%

Sirolimus rescue of renal failure in children after combined liver-kidney transplantation

et al. 2005

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Section: Discussionmentioning

confidence: 99%

Sirolimus rescue of renal failure in children after combined liver-kidney transplantation

et al. 2005

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“…These manifestations occurred mostly with the standard dose administration and blood trough levels (10 -15 ug/L) recommended by foreign experts, and as we know that the adverse reactions are associated with its doses and concentration given, by lowering SRL doses and concentration should be able to reduce or prevent from these adverse reactions to occur; therefore, we think that there could possibly be differences between pharmacokinetic and drug metabolism gene polymorphism as well as genetic background variation in immune system between the Western and Asian population, [15,16] i.e. similar to the administration of cyclsporine, we must not adopt the C2 monitoring standards of European of American renal recipients.…”

Section: Safety Of Srl Conversionmentioning

confidence: 99%

Conversion from Calcineurin Inhibitors to Sirolimus Maintenance Therapy in Renal Allograft Recipients with Risk Factors

Ji¹,

Wen²,

Cheng³

et al. 2011

OJOTS

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Background: The efficacy and safety of conversion treatment with sirolimus in renal transplant recipients using the calcineurin inhibitor (CNI) with one or more risk factors was evaluated. Methods: Ninety-three renal transplant recipients were prospectively enrolled. CNIs(CsA and FK506) as main immunosuppressant were converted to SRL immunosuppressant protocol. Rapid conversion with sirolimus was performed in all patients. The CNI withdrawal was in 2 weeks. At 4 hours after oral administration of cyclosporin A or tacrolimus, the patients took sirolimus. Initial dose of sirolimus was 6 mg, and repeated maintenance dose is 1.0 -2.0 mg/d. The first concentration of sirolimus was detected at 5 -7 days after first oral administration, and the target concentration was 6 -10 μg/L. Results: The symptoms were markedly improved in patients with CNI induced renal toxicity and CNI induced liver toxicity, and the concentration of sirolimus were maintained at (5.1 ± 1.2) μg/L. Serum creatinine levels decreased from (297.72 ± 150.28) μmol/L to (123.76 ± 44.2) μmol/L, and the liver function were recovery in 24 (92.3%) patients. 9 patients with high glucose returned to normal, and 2 patients were improved. Serum creatinine levels decreased more than 25% of primary level in 17 patients, and the effective rate was 51.5%. 10 patients with tumor were appeared 6 -43 months after renal transplantation, no recurrence was found in 8 of them and 2 patients were dead. Acute rejections were occurred in 3 patients at 6 months after conversion treatment. The complications were included hyperlipidemia and proteinuria. 3 patients were dead, 6 patients returned to dialysis treatment, and 2 patients were removal of grafts. At 3 years after conversion treatment, the survival rates of patients and grafts were 90.9% and 75.8%, respectively. Conclusion: The conversion treatment with SRL and MMF may be a better option for the renal transplant recipients using the CNI with risk factors appeared.

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“…The mean apparent clearance rate observed in pediatric renal and small bowel transplant recipients is 8.61Ϯ8.1 mL · min Ϫ1 · kg Ϫ1 or 517 mL · kg Ϫ1 · h Ϫ1 . 28,31 The systemic bioavailability of oral rapamycin is 14%. 32 The CYPHER Select contained 245 g rapamycin, half of which was released within 1 week (ie, 0.73 g/h or 0.24 g · kg Ϫ1 · h Ϫ1 for a 3-kg infant).…”

Section: Rapamycin: Clinical Applicationsmentioning

confidence: 99%

“…20,28,29 In pig models with a DES containing 185 g rapamycin, the whole-blood concentration of the drug peaks at 1 hour (mean, 2.63Ϯ0.74 ng/mL) and then declines below the lower limit of detection by 3 days while achieving therapeutic arterial tissue concentrations. 20 In adults implanted with 150 and 178 g/18 mm DES, peak drug concentration occurred between 3 and 4 hours at a level of 0.57Ϯ0.12 and 1.05Ϯ0.39 ng/mL with 1 or 2 stents, respectively, and minimal measurable blood levels were detectable at day 7.…”

Section: Rapamycin: Clinical Applicationsmentioning

confidence: 99%

Rapamycin-Eluting Stents in the Arterial Duct

et al. 2009

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Background-Maintaining arterial duct patency by stent implantation may be advantageous in congenital heart disease management algorithms. Rapamycin, an immunosuppressant drug that demonstrates antiproliferative properties and inhibits smooth muscle cell migration, may deter the intimal hyperplasia that occurs during spontaneous closure and after-stent implantation of the arterial duct. Methods and Results-Twenty-eight Yorkshire piglets (7 to 11 days old; weight, 2.2 to 4.9 kg) underwent stent implantation of the arterial duct (rapamycin-eluting (nϭ14) or bare metal (nϭ14) stents, 3.5-mm diameter) and were euthanized at 2, 4, and 6 weeks. Dissected arterial ducts were analyzed for lumen diameter, smooth muscle cell, and extracellular matrix components. Isolated arterial duct-derived smooth muscle cells were cultured in the presence or absence of rapamycin. Cellular proliferation rates were assessed by Ki-67 detection and [ 3 H]-thymidine incorporation. No significant neointimal proliferation was present in either stent type at 2 weeks. At 4 weeks, the median luminal diameters of the bare metal stents were 87% (Pϭ0.009), 54% (Pϭ0.004), and 77% (Pϭ0.004) that of the drug-eluting stents at the middle and aortic and pulmonary artery ends, respectively. At 6 weeks, the median luminal diameters of the bare metal stents were 0% (Pϭ0.18), 5% (Pϭ0.25), and 61% (Pϭ0.13) that of the drug-eluting stents at the same respective levels. Complete histological occlusion was found in at least 1 level of the lumen in 9 pigs: 1 (17%) in the BMS group at 4 weeks, 5 (83%) in the BMS group at 6 weeks, and 3 (50%) in the DES group at 6 weeks. In vitro studies demonstrated 50%-lower proliferation rates in rapamycin-treated cultures of duct-derived smooth muscle cell cultures (PϽ0.001). Conclusions-Rapamycin has antiproliferative actions on the arterial duct. Drug-eluting stents may be a more efficient tool than current palliative options for maintaining patency in critically duct-dependent states, but there may be a finite time-related benefit.

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Pharmacokinetics of Sirolimus and Tacrolimus in Pediatric Transplant Patients

Cited by 68 publications

References 33 publications

Sirolimus rescue of renal failure in children after combined liver-kidney transplantation

Sirolimus rescue of renal failure in children after combined liver-kidney transplantation

Conversion from Calcineurin Inhibitors to Sirolimus Maintenance Therapy in Renal Allograft Recipients with Risk Factors

Rapamycin-Eluting Stents in the Arterial Duct

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