Pharmacokinetics/Pharmacodynamics of caspofungin in plasma and peritoneal fluid of liver transplant recipients

2021 ◽  
Author(s):  
Claire Pressiat ◽  
Nawel Ait-Ammar ◽  
Matthieu Daniel ◽  
Anne Hulin ◽  
Françoise Botterel ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Peritoneal Fluid ◽  
Compartment Model ◽  
Transplant Recipients ◽  
Mixed Effect ◽  
First Order ◽  
Transplant Patients ◽  
Two Compartment Model ◽  
Dosing Regimens ◽  
Liver Transplant Recipients

Background: The weaker diffusion of echinocandins in the peritoneal fluid (PF) could promote Candida resistant isolates. The aim of this study was to analyse the pharmacokinetics/pharmacodynamics (PK/PD) of caspofungin in plasma and PF of liver transplant recipients. Methods: Liver transplant patients received caspofungin as postoperative prophylaxis. Caspofungin concentrations were quantified in plasma and in PF on Days 1, 3 and 8. Data were analysed using non-linear mixed-effect modelling and Monte Carlo simulations. Area under curve (AUC) in plasma and PF were simulated under three dosing regimens. Probabilities of target attainment (PTA) were calculated using fAUC 0-24 /minimal inhibitory concentration (MIC) ratios with MICs ranging from 0.008 to 8 mg/litre. All the patients included were monitored weekly for Candida colonisation and for Candida infections. Results: Twenty patients were included. Median daily dose of caspofungin was 0.81 mg/kg. Plasma (n=395) and peritoneal (n=50) concentrations at steady state were available. A two-compartment model with first-order absorption and elimination was described. Our two-compartment model with first-order absorption and elimination model produced an effective PK/PD relationship in plasma, achieving a PTA ≥90% and MIC ranging from 0.008 to 0.12 mg/L for C. albicans and glabrata . In PF, PTAs at D8 were only optimal for a MIC of 0.008 in patients weighing 60 kg under the three dosing regimens. Among the 16 patients colonized, all MIC values were below the maximal concentration (Cmax) in plasma but not in PF. Conclusion: Peritoneal concentrations of caspofungin were low. Simulations showed that the PTA for Candida spp. in PF were not optimal, that might suggesting a potential risk of resistance.

scholarly journals Effect of CYP3A5 on the Once-Daily Tacrolimus Conversion in Stable Liver Transplant Patients

2020 ◽  
Vol 9 (9) ◽  
pp. 2897
Author(s):  
Jong Man Kim ◽  
Je Ho Ryu ◽  
Kwang-Woong Lee ◽  
Suk Kyun Hong ◽  
Kwangho Yang ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Extended Release ◽  
Trough Level ◽  
Pharmacokinetic Analysis ◽  
Transplant Recipients ◽  
Open Label ◽  
Once Daily ◽  
Transplant Patients ◽  
Liver Transplant Recipients ◽  
Cyp3a5 Polymorphism

Cytochrome P450 (CYP) 3A5 polymorphism influences tacrolimus metabolism, but its effect on the drug pharmacokinetics in liver transplant recipients switched to once-daily extended-release formulation remains unknown. The aim of this study is to analyze the effect of CYP3A5 polymorphism on liver function after once-daily tacrolimus conversion in liver transplant patients. A prospective open-label study included 60 stable liver transplant recipients who underwent 1:1 conversion from twice-daily tacrolimus to once-daily tacrolimus. All participants were genotyped for CYP3A5 polymorphism. The study was registered at ClinicalTrials.gov (NCT 02882113). Twenty-eight patients were enrolled in the CYP3A5 expressor group and 32 in the non-expressor group. Although there was no statistical difference, incidence of liver dysfunction was higher in the expressor group than in the non-expressor group when converted to once-daily extended-release tacrolimus (p = 0.088). No biopsy-proven acute rejection, graft failure, and mortality were observed in either group. The decrease in dose-adjusted trough level (−42.9% vs. −26.1%) and dose/kg-adjusted trough level of tacrolimus (−40.0% vs. −23.7%) was significantly greater in the expressor group than in the non-expressors after the conversion. A pharmacokinetic analysis was performed in 10 patients and tacrolimus absorption in the non-expressor group was slower than in the expressor group. In line with this observation, the area under the curve for once-daily tacrolimus correlated with trough level (Cmin) in the non-expressors and peak concentration (Cmax) in the expressors. CYP3A5 genotyping in liver transplant recipients leads to prediction of pharmacokinetics after switching from a twice-daily regimen to a once-daily dosage form, which makes it possible to establish an appropriate dose of tacrolimus.

scholarly journals Detection of human herpesvirus-7 by qualitative nested-PCR: comparison between healthy individuals and liver transplant recipients

2008 ◽  
Vol 41 (6) ◽  
pp. 556-559 ◽  
Author(s):  
Ronaldo Luis Thomasini ◽  
Juliana de Moraes Martins ◽  
Daniela Corte Parola ◽  
Sandra Helena Alves Bonon ◽  
Ilka de Fátima Santana Ferreira Boin ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Healthy Volunteers ◽  
Nested Pcr ◽  
Human Herpesvirus ◽  
Transplant Recipients ◽  
Healthy Individuals ◽  
Active Infection ◽  
Serological Tests ◽  
Transplant Patients ◽  
Liver Transplant Recipients

Diagnosis of human herpesvirus-7 active infection in transplant patients has proved difficult, because this virus is ubiquitous and can cause persistent infections in the host. The significance of viral DNA detected in leukocytes by PCR is unclear and cross-reaction in serological tests may occur. This study aimed to evaluate nested-PCR to detect human herpesvirus-7 active infection in liver transplant recipients compared to healthy individuals. human herpesvirus-7 nested-PCR was performed on leukocytes and sera of 53 healthy volunteers and sera of 29 liver transplant recipients. In healthy volunteers, human herpesvirus-7 was detected in 28.3% of leukocytes and 0% of serum. human herpesvirus-7 was detected in sera of 48.2% of the liver transplant recipients. Nested-PCR on DNA extracted from leukocytes detected latent infection and the study suggests that nested-PCR performed on serum could be useful to detect human herpesvirus-7 active infection in liver transplant recipients.

scholarly journals Profile of a Liver Transplant Follow-Up Clinic in a Nontransplant Canadian Urban Centre

1997 ◽  
Vol 11 (3) ◽  
pp. 235-238 ◽  
Author(s):  
R Bazylewski ◽  
BG Rosser ◽  
A Cohen ◽  
KDE Kaita ◽  
GY Minuk
Keyword(s):  
Liver Transplant ◽  
First Year ◽  
Transplant Recipients ◽  
Urban Centre ◽  
Care Clinic ◽  
Transplant Centre ◽  
Transplant Patients ◽  
Ambulatory Care Clinic ◽  
Liver Transplant Recipients

Care of the growing number of liver transplant recipients will increasingly fall on the referring centres. Thus, there is a need to define more clearly the demographic, clinical and laboratory profiles of liver transplant recipients, particularly in the setting of a centre where a liver transplantation program does not exist. The present study documented these features in 37 patients attending an adult ambulatory care clinic in an urban, nonliver transplant centre. Mean ± SD age of the study population was 44±11.9 years. Twenty-one patients (57%) were male. Annual enrolment in the clinic increased from three patients at the completion of the clinic's first year (1988) to 16 patients in the final year of the study (1993). Time between the transplantation procedure and the patient's return to the referring centre decreased from a mean of 12 weeks in 1988 to four weeks in 1993. During those seven years no patient required an unscheduled return to the transplant centre for surgical complications or problems associated with immunosuppressive therapy. In conclusion, these data provide a profile of liver transplant patients attending a nonliver transplant centre for follow-up and support the concept that nontransplant centres are capable of providing safe and, in terms of travel, less expensive care for liver transplant recipients.

scholarly journals Renal Safety of Tenofovir Disoproxil Fumarate and Entecavir in Liver Transplant Patients: A Nationwide Korean Registry Study

2021 ◽  
Author(s):  
Juhan Lee ◽  
Jae Geun Lee ◽  
Shin Hwang ◽  
Kwang-Woong Lee ◽  
Jong Man Kim ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Transplant ◽  
Renal Dysfunction ◽  
Transplant Recipients ◽  
Post Transplantation ◽  
Transplant Patients ◽  
Increased Risk ◽  
B Virus ◽  
Liver Transplant Recipients ◽  
Renal Safety

Abstract Background and aims: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have been recommended after liver transplantation to prevent recurrence of hepatitis B virus infection. Despite its proven efficacy, the renal safety of TDF has not been established in liver transplant recipients. We aimed to compare the effects of TDF and ETV on renal function in liver transplant recipients and to evaluate risk factors for renal dysfunction after liver transplantation. Methods: This is a retrospective, observational multicenter study of data from the Korean Organ Transplantation Registry. We included adults who underwent liver transplantation for hepatitis B virus-related complications from April 2014 to December 2017 and received TDF or ETV post-transplantation. Renal dysfunction was defined as an estimated glomerular filtration rate decline by at least 20% from baseline (1 month post-transplantation). Median duration of follow-up was 29 months (interquartile range 19–42).Results: A total of 804 liver transplant patients were included. The cumulative probability of renal dysfunction was significantly higher in the TDF group than in the ETV group. Multivariable analysis confirmed that TDF was independently associated with an increased risk of renal dysfunction (hazard ratio = 1.47, 95% confidence interval 1.12-1.92; P = 0.005). Independent risk factors for renal dysfunction included older age, worse baseline renal function, and low body mass index. Renal dysfunction after liver transplantation was independently associated with increased mortality.Conclusions: In this nationwide study, use of TDF was associated with an increased risk of renal dysfunction, when compared with ETV.

scholarly journals Linezolid-Induced Lactic Acidosis in Two Liver Transplant Patients with the Mitochondrial DNA A2706G Polymorphism

2014 ◽  
Vol 58 (7) ◽  
pp. 4227-4229 ◽  
Author(s):  
J. L. Del Pozo ◽  
N. Fernández-Ros ◽  
E. Sáez ◽  
J. I. Herrero ◽  
J. R. Yuste ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Lactic Acidosis ◽  
Liver Transplant ◽  
Underlying Mechanism ◽  
Transplant Recipients ◽  
Mitochondrial Dna Polymorphism ◽  
Transplant Patients ◽  
Liver Transplant Recipients ◽  
First Time

ABSTRACTMitochondrial toxicity has been recently suggested to be the underlying mechanism of long-term linezolid-associated toxicity in patients with 16S rRNA genetic polymorphisms. Here, we report for the first time two cases of lactic acidosis due to long-term linezolid exposure in liver transplant recipients who presented an A2706G mitochondrial DNA polymorphism.

scholarly journals Population Pharmacokinetics of intravenous Ganciclovir and oral Valganciclovir in pediatric population to optimize dosing regimens

2020 ◽  
pp. AAC.02254-20
Author(s):  
T. Nguyen ◽  
M. Oualha ◽  
C. Briand ◽  
M. Bendavid ◽  
A. Béranger ◽  
...  
Keyword(s):  
Pediatric Population ◽  
Preventive Treatment ◽  
Compartment Model ◽  
Critically Ill Children ◽  
Therapeutic Drug ◽  
Intravenous Ganciclovir ◽  
Mixed Effect ◽  
First Order ◽  
Dosing Regimens ◽  
Oral Valganciclovir

Context: Ganciclovir is indicated for curative or preventive treatment of cytomegalovirus (CMV) infections. This study aimed to characterize ganciclovir pharmacokinetics, following intravenous ganciclovir and oral valganciclovir administration, in order to optimize dosing scheme.Method: All children aged <18 years receiving ganciclovir or valganciclovir were included in this study. Pharmacokinetics were described using non-linear mixed-effect modelling. Monte Carlo simulations were used to optimize dosing regimen in order to maintain area under the concentration curve (AUC) in the preventive or therapeutic target.Results: Among the 105 children (374 concentration-time observations) included, 78 received intravenous (IV) ganciclovir, 19 oral valganciclovir and 6 both drugs. A two-compartment model with first-order absorption for valganciclovir and first-order elimination best described the data. An allometric model was used to describe bodyweight (BW) effect. Estimated glomerular filtration rate (eGFR) and critically-ill children medical status were significantly associated with ganciclovir elimination.Conclusion: Recommended doses were adapted for prophylactic treatment. To obtain a therapeutic exposure, doses should be increased to 40 mg/kg/day oral or 15-20 mg/kg/day IV in children with normal eGFR and to 56 mg/kg/day oral or 20-25 mg/kg/day IV in children with augmented eGFR. These doses should be prospectively confirmed and a therapeutic drug monitoring could be used to refine them individually.

Population pharmacokinetics and dosing simulations of amoxicillin in obese adults receiving co-amoxiclav

2020 ◽  
Vol 75 (12) ◽  
pp. 3611-3618
Author(s):  
G Mellon ◽  
K Hammas ◽  
C Burdet ◽  
X Duval ◽  
C Carette ◽  
...  
Keyword(s):  
Compartment Model ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Open Label ◽  
Mixed Effect ◽  
Mean Values ◽  
Two Compartment Model ◽  
Amoxicillin Clavulanate ◽  
Dosing Regimens ◽  
Obese Subjects

Abstract Background Pneumonia, skin and soft tissue infections are more frequent in obese patients and are most often treated by co-amoxiclav, using similar dosing regimens to those used for non-obese subjects. No data are available on amoxicillin pharmacokinetics among obese subjects receiving co-amoxiclav. Materials and methods Prospective, single-centre, open-label, non-randomized, crossover pharmacokinetic trial having enrolled obese otherwise healthy adult subjects. A first dose of co-amoxiclav (amoxicillin/clavulanate 1000/200 mg) was infused IV over 30 min, followed by a second dose (1000/125 mg) administered orally, separated by a washout period of ≥24 h. We assayed concentrations of amoxicillin by a validated ultra HPLC–tandem MS technique. We estimated population pharmacokinetic parameters of amoxicillin by non-linear mixed-effect modelling using the SAEM algorithm developed by Monolix. Results Twenty-seven subjects were included in the IV study, with 24 included in the oral part of the study. Median body weight and BMI were 109.3 kg and 40.6 kg/m2, respectively. Amoxicillin pharmacokinetics were best described by a two-compartment model with first-order elimination. Mean values for clearance, central volume, intercompartmental clearance and peripheral volume were, respectively, 14.6 L/h, 9.0 L, 4.2 L/h and 6.4 L for amoxicillin. Oral bioavailability of amoxicillin was 79.7%. Amoxicillin Cmax after oral administration significantly reduced with weight (P = 0.013). Dosing simulations for amoxicillin predicted that most of the population will achieve the pharmacodynamic target of fT&gt;MIC ≥40% with the regimen of co-amoxiclav 1000/200 mg (IV) or 1000/125 mg (oral) q8h for MICs titrated up to 0.5 mg/L (IV) and 1 mg/L (oral). Conclusions Pharmacokinetic/pharmacodynamic goals for amoxicillin can be obtained in obese subjects.

scholarly journals Immunotherapy with Tacrolimus (FK506) Does Not Select for Resistance to Calcineurin Inhibitors in Candida albicans Isolates from Liver Transplant Patients

2006 ◽  
Vol 50 (4) ◽  
pp. 1573-1577 ◽  
Author(s):  
Jennifer L. Reedy ◽  
Shahid Husain ◽  
Michael Ison ◽  
Timothy L. Pruett ◽  
Nina Singh ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Liver Transplant ◽  
Immunosuppressive Therapy ◽  
Calcineurin Inhibitor ◽  
Calcineurin Inhibitors ◽  
Antifungal Drugs ◽  
Transplant Recipients ◽  
Transplant Patients ◽  
Liver Transplant Recipients

ABSTRACT In Candida albicans, calcineurin mediates tolerance to azole antifungal drugs, survival in serum, and virulence. In this study, we examined 24 Candida isolates from liver transplant recipients receiving a calcineurin inhibitor as a component of their immunosuppressive therapy. We were unable to detect a difference in susceptibility to calcineurin inhibitors in combination with fluconazole, serum, or calcium in these isolates.

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