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Population Pharmaco...
Population Pharmacokinetic and Pharmacodynamic Analysis of Valganciclovir for Optimizing Preemptive Therapy of Cytomegalovirus Infections in Kidney Transplant Recipients
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- Cojutti, Pier Giorgio (författare)
- Univ Bologna, Dept Med & Surg Sci, Alma Mater Studiorum, Bologna, Italy.;IRCCS Azienda Osped Univ Bologna, Clin Pharmacol Unit, Bologna, Italy.
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- Heffernan, Aaron J. (författare)
- Univ Queensland, Fac Med, Ctr Clin Res, Herston, Qld, Australia.
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- Tängdén, Thomas (författare)
- Uppsala universitet,Infektionsmedicin
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- Della Siega, Paola (författare)
- Santa Maria della Misericordia Univ Hosp Udine, ASUFC, Infect Dis Clin, Udine, Italy.
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- Tascini, Carlo (författare)
- Santa Maria della Misericordia Univ Hosp Udine, ASUFC, Infect Dis Clin, Udine, Italy.
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- Roberts, Jason A. (författare)
- Univ Queensland, Fac Med, Ctr Clin Res, Herston, Qld, Australia.;Royal Brisbane & Womens Hosp, Dept Pharm, Brisbane, Qld, Australia.;Metro North Hlth, Herston Infect Dis Inst HeIDI, Brisbane, Qld, Australia.;Royal Brisbane & Womens Hosp, Dept Intens Care Med, Brisbane, Qld, Australia.;Univ Montpellier, Nimes Univ Hosp, Div Anaesthesiol Crit Care Emergency & Pain Med, Nimes, France.
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- Pea, Federico (författare)
- Univ Bologna, Dept Med & Surg Sci, Alma Mater Studiorum, Bologna, Italy.;IRCCS Azienda Osped Univ Bologna, Clin Pharmacol Unit, Bologna, Italy.
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Univ Bologna, Dept Med & Surg Sci, Alma Mater Studiorum, Bologna, Italy;IRCCS Azienda Osped Univ Bologna, Clin Pharmacol Unit, Bologna, Italy. Univ Queensland, Fac Med, Ctr Clin Res, Herston, Qld, Australia. (creator_code:org_t)
- 2023-02-23
- 2023
- Engelska.
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Ingår i: Antimicrobial Agents and Chemotherapy. - : American Society for Microbiology. - 0066-4804 .- 1098-6596. ; 67:3
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- This study aimed to develop a population pharmacokinetic/pharmacodynamic (PK/PD) model of valganciclovir for preemptive therapy of cytomegalovirus (CMV) infection in kidney transplant patients. A population PK/PD model was developed with Monolix. Ganciclovir concentrations and CMV viral loads were obtained retrospectively from kidney transplant patients receiving routine clinical care. Ten thousand Monte Carlo simulations were performed with the licensed dosages adjusted for renal function to assess the probability of attaining a viral load target of <= 290 and <= 137 IU/mL. Fifty-seven patients provided 343 ganciclovir concentrations and 328 CMV viral loads for PK/PD modeling. A one-compartment pharmacokinetic model coupled with an indirect viral turnover growth model with stimulation of viral degradation pharmacodynamic model was devised. Simulations showed that 1- and 2-log(10) reduction of CMV viral load mostly occurred between a median of 5 to 6 and 12 to 16 days, respectively. The licensed dosages achieved a probability of reaching the viral load target >= 90% at days 35 to 49 and 42 to 56 for the thresholds of <= 290 and <= 137 IU/mL, respectively. Simulations indicate that in patients with an estimated glomerular filtration rate of 10 to 24 mL/min/1.73m(2), a dose increase to 450 mg every 36 h may reduce time to optimal viral load target to days 42 and 49 from a previous time of 49 and 56 days for the thresholds of <= 290 and <= 137 IU/mL, respectively. Currently licensed dosages of valganciclovir for preemptive therapy of CMV infection may achieve a viral load reduction within the first 2 weeks, but treatment should continue for >= 35 days to ensure viral load suppression.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- cytomegalovirus
- kidney transplant
- valganciclovir PK
- PD
- preemptive therapy
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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