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Population pharmacokinetics of tacrolimus in paediatric haematopoietic stem cell transplant recipients : New initial dosage suggestions and a model based dosage adjustment tool
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- Wallin, Johan, 1974- (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmacometrics
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- Friberg, Lena (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Pharmacometrics
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- Fasth, Anders (författare)
- Department of Paediatrics, University of Gothenburg, Gothenburg, Sweden,Immunology
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- (creator_code:org_t)
- Philadelphia PA, US : Lippincott Williams & Wilkins, 2009
- 2009
- Engelska.
- Ingår i: Therapeutic Drug Monitoring. - Philadelphia PA, US : Lippincott Williams & Wilkins. - 0163-4356 .- 1536-3694. ; 31:4, s. 457-466
- Tidskriftsartikel (refereegranskat)
Abstract
Ämnesord
Stäng
- The population pharmacokinetics of tacrolimus was described in 22 paediatric haematopoietic stem cell transplant recipients and a model-based dosage adjustment tool that may assist with therapy in new patients was developed. Patients received tacrolimus by continuous intravenous infusion (0.03mg/kg/day) starting two days before transplantation, with conversion to oral therapy 2-3 weeks post-transplant. Population pharmacokinetic analysis was performed using NONMEM. A dosage adjustment tool that searches for individual parameter estimates to describe concentration measurements, counter-balanced by the final population model, was created in Excel. Typical clearance was 106 mL/h/kg0.75, typical distribution volume was 3.71 L/kg and typical bioavailability was 15.7%. Tacrolimus clearance decreased with increasing serum creatinine and bioavailability decreased with post-operative day. Predictions from the model showed that current intravenous dose recommendations of 0.03 mg/kg/day may produce potentially toxic drug concentrations in the patient population, whereas current oral conversion of four times the adjusted intravenous dose may lead to subtherapeutic concentrations. We suggest a dose of 0.035mg/kg0.75/day to ensure satisfactory levels, and an oral conversion factor of six times the intravenous dose. A dosage adjustment tool was developed that is capable of suggesting an initial infusion rate based on patient weight and serum creatinine and of devising a further individualised dosage as individual drug concentration measurements become available. The tool also allows the clinicia to graphically examine the concentration-time profile of tacrolimus under different infusion rates, with or without a loading dose.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- tacrolimus
- pediatric hematopoietic stem cell transplant
- population pharmacokinetics
- Bayesian forecasting
- dosage prediction
- PHARMACY
- FARMACI
- Pharmacokinetics and Drug Therapy
- Farmakokinetik och läkemedelsterapi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Therapeutic Drug Monitoring (Sök värdpublikationen i LIBRIS)
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