Pharmacokinetic Interaction Between Amprenavir/Ritonavir and FosAmprenavir on Cyclosporine in Two Patients With Human Immunodeficiency Virus Infection Undergoing Orthotopic Liver Transplantation

Guaraldi, Giovanni; Cocchi, Stefania; Codeluppi, Mauro; Benedetto, Fabrizio Di; Bonora, Stefano; Motta, A.; Luzi, Kety; Pecorari, Monica; Gennari, William; Masetti, Michele; Gerunda, G.E.; Esposito, Roberto

doi:10.1016/j.transproceed.2006.02.013

Cited by 17 publications

(10 citation statements)

References 6 publications

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“…In patients on tacrolimus or sirolimus, not only was the immunosuppressant dose markedly decreased, but the dosing interval increased more than five-fold. Similar findings have been demonstrated by other investigators in liver transplant recipients 52,53,54,55. Notably, azole antifungals and macrolide antibiotics also inhibit the CYP3A4 system 56…”

Section: Drug Interactionssupporting

confidence: 89%

Renal transplantation in patients with HIV

2009

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HIV infection has been a major global health problem for almost three decades. With the introduction of highly active anti-retroviral therapy in 1996, and the advent of effective prophylaxis and management of opportunistic infections, AIDS mortality has decreased markedly. In developed countries, this once fatal infection is now being treated as a chronic condition. As a result, rate of morbidity and mortality from other medical conditions leading to end-stage liver, kidney and heart disease is steadily increasing in individuals with HIV. Presence of HIV infection used to be viewed as a contraindication to transplantation for multiple reasons:,concerns for exacerbation of an already immunocompromised state by administration of additional immunosuppressants; the use of a limited supply of donor organs with unknown long-term outcomes; and, the risk of viral transmission to the surgical and medical staff. This Review examines open questions on kidney transplantation in patients infected with HIV-1 and clinical strategies that have resulted in good outcomes. It also describes the clinical concerns associated with the treatment of renal transplant recipients with HIV.

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Section: Drug Interactionssupporting

confidence: 89%

Renal transplantation in patients with HIV

2009

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“…This current study contains the largest set of pharmacokinetic interaction data between HAART and immunosuppressant agents reported over the longest period of time in HIV‐infected transplant subjects. Although smaller studies of tacrolimus and CsA have reported dose adjustments in both liver and kidney transplant patients with HIV on various ARV therapies, this is the first study that we know of that documents changes in pharmacokinetics over time.…”

Section: Discussionmentioning

confidence: 93%

“…With the increasing experience with transplantation in HIV‐infected subjects with end stage liver and kidney disease, we and others have shown that antiretroviral (ARV) protease inhibitors (PIs) and non‐nucleoside reverse transcriptase inhibitors (NNRTIs) can alter the pharmacokinetics and dosing requirements for calcineurin inhibitor immunosuppressants (ISs), such as cyclosporine (CsA) and tacrolimus (TAC), and other medications with similar metabolic pathways . The HIV PIs used as ARV therapy and the ISs are substrates and inhibitors of the cytochrome P450 metabolizing enzyme CYP3A4 (CYP3A4) and can increase the systemic blood levels of each class of medication .…”

Section: Introductionmentioning

confidence: 99%

Changes in clearance, volume and bioavailability of immunosuppressants when given with HAART in HIV‐1 infected liver and kidney transplant recipients

Frassetto

Floren

Barin

et al. 2013

Biopharm & Drug Disp

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Solid organ transplantation in Human Immunodeficiency Virus 1 (HIV)-infected individuals requiring concomitant use of immunosuppressants (IS) [e.g., cyclosporine (CsA) or tacrolimus (TAC)] and antiretrovirals (ARVs) [e.g., protease inhibitors (PIs) and/or non-nucleoside reverse transcriptase inhibitors (NNRTIs)] is complicated by significant drug interactions. We describe the pharmacokinetics of CsA and TAC in 52 patients on both IS and NNRTIs, PIs, or combined NNRTIs+PIs, in studies conducted at 2 weeks, 3, 6, 12 and 24 months after transplantation. CsA and TAC blood concentrations were measured by LC/MS/MS. This multisubject, varied ARV-IS drug combination, longitudinal observational patient study provided a unique opportunity to examine the effect of different ARV drugs on IS PK by comparing ratios of parameters over time and between PK parameters. Subjects taking concomitant PIs exhibited increases in CsA and TAC exposure (AUC/dose) due to increased apparent oral bioavailability and decreased apparent oral clearance. Those subjects taking CsA and concomitant efavirenz (EFV) showed time dependent increases in exposure due to ~30% increases in apparent oral bioavailability over time as well as decreased apparent oral clearance, while subjects on TAC and EFV showed time-dependent changes in all PK parameters. The increased bioavailability was not observed in patients on CsA and nevirapine (NVP). These differences between IS drugs and the changes in PK parameters are not easily predicted, illustrating the importance of continued therapeutic drug monitoring in these patients on these complex medication regimens.

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“…36,38,[42][43][44][45][46][47][48][49][50] Moreover, in patients on RTV-boosted PIs even higher drastic dosage reductions up to 120-fold are necessary to achieve therapeutic through levels of tacrolimus, cyclosporine, and sirolimus. 7,35,37,38,42,45,47,[51][52][53][54][55][56][57][58][59][60][61][62][63][64] Initiation of a posttransplant CNI dosing strategy similar to that used in a non-HIV positive patient can immediate lead to extremely high persistent CNI inhibitor levels and concurrent (nephro)toxicity [59]. CNI half life is prolonged 5-to 20-fold because of the systemic inhibition of CYP 3A and Pgp, resulting in dosing regimens of 0.5-1 mg once weekly for tacrolimus and 25 mg every 1-2 days for cyclosporine in kidney and liver transplant recipients.…”

Section: Protease Inhibitorsmentioning

confidence: 99%

Drug–Drug Interactions Between Antiretroviral and Immunosuppressive Agents in HIV-Infected Patients After Solid Organ Transplantation: A Review

Maarseveen

Rogers

Trofe‐Clark

et al. 2012

AIDS Patient Care and STDs

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Since the introduction of combination antiretroviral therapy (cART) resulting in the prolonged survival of HIV-infected patients, HIV infection is no longer considered to be a contraindication for solid organ transplantation (SOT). The combined management of antiretroviral and immunosuppressive therapy proved to be extremely challenging, as witnessed by high rates of allograft rejection and drug toxicity, but the profound drug-drug interactions between immunosuppressants and cART, especially protease inhibitors (PIs) also play an important role. Caution and frequent drug level monitoring of calcineurin inhibitors, such as tacrolimus are necessary when PIs are (re)introduced or withdrawn in HIV-infected recipients. Furthermore, the pharmacokinetics of glucocorticoids and mTOR inhibitors are seriously affected by PIs. With the introduction of integrase inhibitors, CCR5-antagonists and fusion inhibitors which cause significantly less pharmacokinetic interactions, have minor overlapping toxicity, and offer the advantage of pharmacodynamic synergy, it is time to revaluate what may be considered the optimal antiretroviral regimen in SOT recipients. In this review we provide a brief overview of the recent success of SOT in the HIV population, and an update on the pharmacokinetic and pharmacodynamic interactions between currently available cART and immunosuppressants in HIV-infected patients, who underwent SOT.

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Pharmacokinetic Interaction Between Amprenavir/Ritonavir and FosAmprenavir on Cyclosporine in Two Patients With Human Immunodeficiency Virus Infection Undergoing Orthotopic Liver Transplantation

Cited by 17 publications

References 6 publications

Renal transplantation in patients with HIV

Renal transplantation in patients with HIV

Changes in clearance, volume and bioavailability of immunosuppressants when given with HAART in HIV‐1 infected liver and kidney transplant recipients

Drug–Drug Interactions Between Antiretroviral and Immunosuppressive Agents in HIV-Infected Patients After Solid Organ Transplantation: A Review

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