Renal transplantation in an HIV-infected patient: Pharmacokinetic aspects

Alstrup, Karen; Kangas, Ida; Laursen, Alex Lund; Jørgensen, Kaj Anker

doi:10.3109/00365599.2010.548081

Cited by 5 publications

(3 citation statements)

References 14 publications

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“…To date, only very small studies of the effects of ARVs on IS have been reported, and most of those patients did not have repeat studies over time. (7, 8, 9, 10)…”

Section: Introductionmentioning

confidence: 99%

Best Single Time Point Correlations With AUC for Cyclosporine and Tacrolimus in HIV-Infected Kidney and Liver Transplant Recipients

et al. 2014

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Background Interactions between antiretrovirals (ARVs) and transplant immunosuppressant agents (IS) among HIV-infected transplant recipients may lead to lack of efficacy or toxicity. In transplant recipients not infected with HIV, cyclosporine (CsA) and tacrolimus (TAC) trough levels (C0) or those drawn two hours after dosing (C2) correlate with drug exposure (AUC/dose) and outcomes. Due to ARV-IS interactions in HIV-infected individuals, and the high rate of rejection in these subjects, we investigated the correlations between IS concentrations and exposure to determine the best method to monitor immunosuppressant levels. Methods We prospectively studied 50 HIV-infected transplant recipients undergoing kidney or liver transplantation evaluating the pharmacokinetics of the IS over time after transplantation (weeks 2 to 4, 12, 28, 52, and 104). IS levels were measured with LC/MS/MS and AUC calculated using WinNonLin 9.0. Correlation analyses were run on SAS 9.2 Results CsA concentration at C4 correlated better with AUC than C0 or C2, and TAC concentration correlated better at C0 or C2. Conclusions We suggest that C0 is acceptable for TAC monitoring, but poor predictability will occur at C0 with CsA. The low correlation of C0 with CsA AUC could be responsible for the higher rejection rates on CsA that has been reported in these subjects.

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“…To date, only very small studies of the effects of ARVs on IS have been reported, and most of those patients did not have repeat studies over time. (7, 8, 9, 10)…”

Section: Introductionmentioning

confidence: 99%

Best Single Time Point Correlations With AUC for Cyclosporine and Tacrolimus in HIV-Infected Kidney and Liver Transplant Recipients

et al. 2014

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“…Nonetheless, recent guidelines provide essential guidance on starting dose ranges for some IS agents when combined with boosted PIs 8 and a few studies have evaluated the use of pharmacokinetic modeling to manage drug interactions between ARV and IS agents. [49][50][51][52][53] More study is also needed to improve long-term outcomes and prevent toxicity from both IS and ARV therapies. For instance, when compared with cyclosporine in HIV-infected kidney transplant recipients, the use of tacrolimus was associated with a reduced risk of acute rejection.…”

Section: Discussionmentioning

confidence: 99%

Pharmacotherapeutic Interventions in People Living With HIV Undergoing Solid Organ Transplantation: A Scoping Review

Lam

Moussa

Sakr

et al. 2023

Transplantation Direct

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Background. The pharmacotherapeutic management of people living with HIV (PLWHIV) undergoing solid organ transplantation (SOT) is clinically challenging, mainly due to the frequent occurrence of complex drug–drug interactions. Although various strategies have been proposed to improve treatment outcomes in these patients, several uncertainties remain, and consensus practice guidelines are just beginning to emerge. The main objective of this scoping review was to map the extent of the literature on the pharmacotherapeutic interventions performed by healthcare professionals for PLWHIV undergoing SOT. Methods. We searched Medline, Embase, and the Cochrane databases as well as gray literature for articles published between January 2010 and February 2020. Study selection was performed by at least 2 independent reviewers. Articles describing pharmacotherapeutic interventions in PLWHIV considered for or undergoing SOT were included in the study. Results. Of the 12 599 references identified through our search strategy, 209 articles met the inclusion criteria. Results showed that the vast majority of reported pharmacotherapeutic interventions concerned the management of immunosuppressive and antimicrobial therapy, including antiretrovirals. Analysis of the data demonstrated that for several aspects of the pharmacotherapeutic management of PLWHIV undergoing SOT, there were differing practices, such as the choice of immunosuppressive induction and maintenance therapy. Other important aspects of patient management, such as patient counseling, were rarely reported. Conclusions. Our results constitute an extensive overview of current practices in the pharmacotherapeutic management of SOT in PLWHIV and identify knowledge gaps that should be addressed to help improve patient care in this specific population.

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“…To date, only very small studies of the effects of ARVs on IS have been reported, and most of those patients did not have repeat studies over time. (7,8,9,10) In non-HIV kidney and liver transplantation, trough (C0) or C2 levels are used to monitor levels of cyclosporine (CsA) and tacrolimus (TAC), two of the most commonly used immunosuppressant drugs, because the level of IS at these time points correlate with AUC and outcomes (11). In HIV transplant, whether these levels correlate with outcomes or toxicity is still unclear (6,12).…”

Section: Introductionmentioning

confidence: 99%

Effect of P-Glycoprotein on the Rat Intestinal Permeability and Metabolism of the BDDCS Class 1 Drug Verapamil

et al. 2013

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The Biopharmaceutics Drug Disposition Classification System (BDDCS) predicts intestinal transporter effects to be clinically insignificant following oral dosing for highly soluble and highly permeable/metabolized drugs (class 1 drugs). We investigated the effect of inhibiting P-glycoprotein (P-gp) on the in vitro rat intestinal permeability (Papp) and metabolism of the class 1 drug verapamil. Jejunal segments from Sprague-Dawley rats fasted overnight were mounted in Ussing chambers filled with 10 mL of Krebs-Ringer buffer (KRB). For P-gp inhibition studies, GG918 0.5 μM was added to the KRB solution. The experiment started by the addition of verapamil (1 or 10 μM) to either apical or basolateral sides. Samples from verapamil donor and receiver compartments were collected at 30 s and 0.166, 0.5, 1, 1.83 and 3 h after the start of the experiment. Analysis of verapamil and its major metabolite, norverapamil, in the samples and intracellularly at 3 h was performed by HPLC. The same experiment was repeated with norverapamil 10 μM (verapamil metabolite), digoxin 100 nM (positive control for P-gp activity) and atorvastatin 1 and 10 μM (example of a class 2 drug). For 1 μM verapamil, efflux ratio (B to A Papp/A to B Papp) was 4.6 and markedly decreased by GG918 (efflux ratio = 1.1). For 10 μM verapamil efflux ratio was 4.1 (control) vs 1.8 (GG918), comparable to the change seen for digoxin 100 nM with an efflux ratio of 3.6 (control) vs 1.6 (with GG918) and atorvastatin (efflux ratio of 5.2 and 3.0 for atorvastatin 1.0 and 10 μM, respectively, changed to 1.0 and 0.65 with GG918). The changes observed in the norverapamil 10 μM experiment were also significant, where efflux ratio decreased from 13.5 (control) to 1.5 (GG918). The extraction ratio (ER) of 10 μM verapamil to norverapamil decreased from 0.41 after an apical dose to 0.21 after a basolateral dose, but was unaffected by the incubation with GG918. The results suggest that P-gp inhibition has an effect on class 1 drug verapamil and class 2 drug atorvastatin Papp in the rat intestine. Moreover, a stronger P-gp effect on the Papp of the more polar norverapamil metabolite was observed. Papp changes caused by the P-gp inhibitor GG918 do not affect the extent of verapamil metabolism.

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Renal transplantation in an HIV-infected patient: Pharmacokinetic aspects

Cited by 5 publications

References 14 publications

Best Single Time Point Correlations With AUC for Cyclosporine and Tacrolimus in HIV-Infected Kidney and Liver Transplant Recipients

Best Single Time Point Correlations With AUC for Cyclosporine and Tacrolimus in HIV-Infected Kidney and Liver Transplant Recipients

Pharmacotherapeutic Interventions in People Living With HIV Undergoing Solid Organ Transplantation: A Scoping Review

Effect of P-Glycoprotein on the Rat Intestinal Permeability and Metabolism of the BDDCS Class 1 Drug Verapamil

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