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Drop in trough blood concentrations of tacrolimus after switching from nelfinavir to fosamprenavir in four HIV-infected liver transplant patients
- Source :
- Scopus-Elsevier
- Publication Year :
- 2008
-
Abstract
- Solid organ transplantation in HIV-infected individuals requires concomitant use of immunosuppressants and antiretrovirals that may cause significant drug interactions. Here we report on a peculiar pharmacokinetic interaction between tacrolimus and protease inhibitors (Pls) which occurred in four HIV-infected liver transplant patients who had to shift Pl therapy from nelfinavir to fosamprenavir as a consequence of regulatory restrictions. After the switch, tacrolimus trough blood concentrations significantly dropped in all patients (mean +/-(SD) 6.9 +/- 2.6 versus 3.2 +/- 2.0 ng/ml before and after the switch, respectively; P=0.01), so that a marked dosage increase was needed (0.29 +/- 0.14 versus 0.88 +/- 0.48 mg/day, 1-3 days before and 3 weeks after the switch, respectively; P=0.046) to attain the desired target (8.7 +/- 2.3 ng/ml). Consistently, marked changes of the concentration/dose ratio of tacrolimus were observed in all cases (27.2 +/- 93 ng/ml per mg/kg/day versus 9.7 4.0 ng/ml per mg/kg/day before and after the switch, respectively; P < 0.001). Our findings suggest that fosamprenavir may be less potent than nelfinavir in inhibiting tacrolimus clearance and support the need for higher tacrolimus dosage to avoid insufficient immunosuppression in HIV-infected liver transplant patients when switching from nelfinavir to fosamprenavir or even when directly starting antiretroviral therapy with fosamprenavir.
- Subjects :
- Pharmacology
Adult
Male
Sulfonamides
Nelfinavir
Dose-Response Relationship, Drug
HIV Infections
HIV Protease Inhibitors
Middle Aged
Drug Administration Schedule
Organophosphates
Tacrolimus
Liver Transplantation
Infectious Diseases
Humans
Pharmacology (medical)
Drug Interactions
Female
Carbamates
Furans
Immunosuppressive Agents
Subjects
Details
- ISSN :
- 13596535
- Volume :
- 13
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Antiviral therapy
- Accession number :
- edsair.doi.dedup.....0b60573ddf81a7dea98932be1563e563