Population Pharmacokinetics of Intravenous Acyclovir in Oncologic Pediatric Patients
Background: Acyclovir represents the first-line prophylaxis and therapy for herpes virus infections. However, its pharmacokinetics in children exposes them to the risk of ineffective or toxic concentrations. The study was aimed at investigating the population pharmacokinetics (POP/PK) of intravenous...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.865871/full |
| _version_ | 1818489354328211456 |
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| author | Natalia Maximova Daniela Nisticò Giacomo Luci Roberto Simeone Elisa Piscianz Ludovica Segat Egidio Barbi Egidio Barbi Antonello Di Paolo |
| author_facet | Natalia Maximova Daniela Nisticò Giacomo Luci Roberto Simeone Elisa Piscianz Ludovica Segat Egidio Barbi Egidio Barbi Antonello Di Paolo |
| author_sort | Natalia Maximova |
| collection | DOAJ |
| description | Background: Acyclovir represents the first-line prophylaxis and therapy for herpes virus infections. However, its pharmacokinetics in children exposes them to the risk of ineffective or toxic concentrations. The study was aimed at investigating the population pharmacokinetics (POP/PK) of intravenous (IV) acyclovir in oncologic children.Methods: Patients (age, 8.6 ± 5.0 years, 73 males and 47 females) received IV acyclovir for prophylaxis (n = 94) and therapy (n = 26) under a therapeutic drug monitoring (i.e., minimum and maximal plasma concentrations, >0.5 and <25 mg/L, respectively). Plasma concentrations were fitted by nonlinear mixed effect modeling and a simulation of dosing regimens was performed. Findings were stratified according to an estimated glomerular filtration rate (eGFR) threshold of 250 ml/min/1.73 m2.Results: The final 1-compartment POP/PK model showed that eGFR had a significant effect on drug clearance, while allometric body weight influenced both clearance and volume of distribution. The population clearance (14.0 ± 5.5 L/h) was consistent across occasions. Simulation of standard 1-h IV infusion showed that a 10-mg/kg dose every 6 h achieved target concentrations in children with normal eGFR (i.e., ≤250 ml/min/1.73 m2). Increased eGFR values required higher doses that led to an augmented risk of toxic peak concentrations. On the contrary, simulated prolonged (i.e., 2 and 3-h) or continuous IV infusions at lower doses increased the probability of target attainment while reducing the risk of toxicities.Conclusion: Due to the variable pharmacokinetics of acyclovir, standard dosing regimens may not be effective in some patients. Prospective trials should confirm the therapeutic advantage of prolonged and continuous IV infusions |
| first_indexed | 2024-12-10T17:02:46Z |
| format | Article |
| id | doaj.art-b70f40f7dfe44a40aa3aceeaf2d00544 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-10T17:02:46Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-b70f40f7dfe44a40aa3aceeaf2d005442022-12-22T01:40:32ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-04-011310.3389/fphar.2022.865871865871Population Pharmacokinetics of Intravenous Acyclovir in Oncologic Pediatric PatientsNatalia Maximova0Daniela Nisticò1Giacomo Luci2Roberto Simeone3Elisa Piscianz4Ludovica Segat5Egidio Barbi6Egidio Barbi7Antonello Di Paolo8Department of Pediatrics, Institute for Maternal and Child Health—IRCCS Burlo Garofolo, Trieste, ItalyDepartment of Medical, Surgical and Health Sciences, University of Trieste, Trieste, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyTransfusion Medicine Department, Azienda Sanitaria Universitaria “Giuliano Isontina”, Trieste, ItalyLaboratory for Hygiene and Public Health, University Hospital of Trieste, Trieste, ItalyLaboratory for Hygiene and Public Health, University Hospital of Trieste, Trieste, ItalyDepartment of Pediatrics, Institute for Maternal and Child Health—IRCCS Burlo Garofolo, Trieste, ItalyDepartment of Medical, Surgical and Health Sciences, University of Trieste, Trieste, ItalyDepartment of Clinical and Experimental Medicine, University of Pisa, Pisa, ItalyBackground: Acyclovir represents the first-line prophylaxis and therapy for herpes virus infections. However, its pharmacokinetics in children exposes them to the risk of ineffective or toxic concentrations. The study was aimed at investigating the population pharmacokinetics (POP/PK) of intravenous (IV) acyclovir in oncologic children.Methods: Patients (age, 8.6 ± 5.0 years, 73 males and 47 females) received IV acyclovir for prophylaxis (n = 94) and therapy (n = 26) under a therapeutic drug monitoring (i.e., minimum and maximal plasma concentrations, >0.5 and <25 mg/L, respectively). Plasma concentrations were fitted by nonlinear mixed effect modeling and a simulation of dosing regimens was performed. Findings were stratified according to an estimated glomerular filtration rate (eGFR) threshold of 250 ml/min/1.73 m2.Results: The final 1-compartment POP/PK model showed that eGFR had a significant effect on drug clearance, while allometric body weight influenced both clearance and volume of distribution. The population clearance (14.0 ± 5.5 L/h) was consistent across occasions. Simulation of standard 1-h IV infusion showed that a 10-mg/kg dose every 6 h achieved target concentrations in children with normal eGFR (i.e., ≤250 ml/min/1.73 m2). Increased eGFR values required higher doses that led to an augmented risk of toxic peak concentrations. On the contrary, simulated prolonged (i.e., 2 and 3-h) or continuous IV infusions at lower doses increased the probability of target attainment while reducing the risk of toxicities.Conclusion: Due to the variable pharmacokinetics of acyclovir, standard dosing regimens may not be effective in some patients. Prospective trials should confirm the therapeutic advantage of prolonged and continuous IV infusionshttps://www.frontiersin.org/articles/10.3389/fphar.2022.865871/fullacyclovirpediatric patientshematopoietic stem cell transplantationpharmacokineticsnon-linear mixed effect modelingprolonged infusion acyclovir |
| spellingShingle | Natalia Maximova Daniela Nisticò Giacomo Luci Roberto Simeone Elisa Piscianz Ludovica Segat Egidio Barbi Egidio Barbi Antonello Di Paolo Population Pharmacokinetics of Intravenous Acyclovir in Oncologic Pediatric Patients Frontiers in Pharmacology acyclovir pediatric patients hematopoietic stem cell transplantation pharmacokinetics non-linear mixed effect modeling prolonged infusion acyclovir |
| title | Population Pharmacokinetics of Intravenous Acyclovir in Oncologic Pediatric Patients |
| title_full | Population Pharmacokinetics of Intravenous Acyclovir in Oncologic Pediatric Patients |
| title_fullStr | Population Pharmacokinetics of Intravenous Acyclovir in Oncologic Pediatric Patients |
| title_full_unstemmed | Population Pharmacokinetics of Intravenous Acyclovir in Oncologic Pediatric Patients |
| title_short | Population Pharmacokinetics of Intravenous Acyclovir in Oncologic Pediatric Patients |
| title_sort | population pharmacokinetics of intravenous acyclovir in oncologic pediatric patients |
| topic | acyclovir pediatric patients hematopoietic stem cell transplantation pharmacokinetics non-linear mixed effect modeling prolonged infusion acyclovir |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.865871/full |
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