Relationship between CYP3A5 Polymorphism and Tacrolimus Blood Concentration Changes in Allogeneic Hematopoietic Stem Cell Transplant Recipients during Continuous Infusion

A polymorphism in the gene encoding the metabolic enzyme cytochrome P450 family 3 subfamily A member 5 (CYP3A5) is a particularly influential factor in the use of tacrolimus in Japanese patients. Those who are homozygotic for the *3 mutation lack CYP3A5 activity, which results in substantial individual differences in tacrolimus metabolism. The aim of this study was to analyze the relationship between individual differences in tacrolimus blood concentration changes and CYP3A5 polymorphisms in allogeneic hematopoietic stem cell transplantation recipients during the period of increasing blood concentration of the drug following treatment onset. This was a prospective observational cohort study, involving 20 patients administered tacrolimus by continuous infusion. The subjects were divided into the *1/*3 and *3/*3 groups based on CYP3A5 polymorphism analysis. The tacrolimus blood concentration/dose (C/D) ratio increased from day 1 and was largely stable on day 5, and a significant difference was observed between the *1/*3 and *3/*3 groups in the time course of the C/D ratio during this period (p < 0.05). This study reveals the effects of CYP3A5 polymorphism on continuous changes in tacrolimus blood concentration.

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Continuous Infusion Foscarnet Facilitates Administration in Hematopoietic Stem Cell Transplant Patients

Transplantation and Cellular Therapy ◽

10.1016/j.jtct.2021.03.018 ◽

2021 ◽

Author(s):

Walter Domingo ◽

Isabelle T. Nguyen ◽

Joyce J. Johnsrud ◽

Janice (Wes) Brown

Keyword(s):

Stem Cell ◽

Continuous Infusion ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Transplant Patients

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Pharmacokinetics and Pharmacodynamics of Continuous-Infusion Meropenem in Pediatric Hematopoietic Stem Cell Transplant Patients

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00787-15 ◽

2015 ◽

Vol 59 (9) ◽

pp. 5535-5541 ◽

Cited By ~ 6

Author(s):

Piergiorgio Cojutti ◽

Natalia Maximova ◽

Federico Pea

Keyword(s):

Stem Cell ◽

Continuous Infusion ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem Cell Transplant ◽

Stem Cell Transplant ◽

Predictive Performance ◽

Therapeutic Drug ◽

Cell Transplant ◽

Hematopoietic Stem ◽

Gram Negative

ABSTRACTThis study explored the pharmacokinetics and the pharmacodynamics of continuous-infusion meropenem in a population of pediatric hematopoietic stem cell transplant (HSCT) patients who underwent therapeutic drug monitoring. The relationship between meropenem clearance (CLM) and estimated creatinine clearance (CLCR) was assessed by nonlinear regression. A Monte Carlo simulation was performed to investigate the predictive performance of five dosing regimens (15 to 90 mg/kg of body weight/day) for the empirical treatment of severe Gram-negative-related infections in relation to four different categories of renal function. The optimal target was defined as a probability of target attainment (PTA) of ≥90% at steady-state concentration-to-MIC ratios (CSS/MIC) of ≥1 and ≥4 for MICs of up to 8 mg/liter. A total of 21 patients with 44 meropenemCSSwere included. A good relationship between CLMand estimated CLCRwas observed (r2= 0.733). Simulations showed that at an MIC of 2 mg/liter, the administration of continuous-infusion meropenem at doses of 15, 30, 45, and 60 mg/kg/day may achieve a PTA of ≥90% at aCSS/MIC ratio of ≥4 in the CLCRcategories of 40 to <80, 80 to <120, 120 to <200, and 200 to <300 ml/min/1.73 m2, respectively. At an MIC of 8 mg/liter, doses of up to 90 mg/kg/day by continuous infusion may achieve optimal PTA only in the CLCRcategories of 40 to <80 and 80 to <120 ml/min/1.73 m2. Continuous-infusion meropenem at dosages up to 90 mg/kg/day might be effective for optimal treatment of severe Gram-negative-related infections in pediatric HSCT patients, even when caused by carbapenem-resistant pathogens with an MIC of up to 8 mg/liter.

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